Displaying publications 1 - 20 of 42 in total

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  1. Epigenetics: The master control of endothelial cell fate in cancer
    V Subramaniam A, Yehya AHS, Cheng WK, Wang X, Oon CE
    Life Sci, 2019 Sep 01;232:116652.
    PMID: 31302197 DOI: 10.1016/j.lfs.2019.116652
    The development of new blood vessels from pre-existing vasculature is called angiogenesis. The growth of tumors depends on a network of supplying vessels that provide them with oxygen and nutrients. Pro-angiogenic factors that are secreted by tumors will trigger the sprouting of nearby existing blood vessels towards themselves and therefore researchers have developed targeted therapy towards these pro-angiogenic proteins to inhibit angiogenesis. However, certain pro-angiogenic proteins tend to bypass the inhibition. Thus, instead of targeting these expressed proteins, research towards angiogenesis inhibition had been focused on a deeper scale, epigenetic modifications. Epigenetic regulatory mechanisms are a heritable change in a sequence of stable but reversible gene function modification yet do not affect the DNA primary sequence directly. Methylation of DNA, modification of histone and silencing of micro-RNA (miRNA)-associated gene are currently considered to initiate and sustain epigenetic changes. Recent findings on the subject matter have provided an insight into the mechanism of epigenetic modifications, thus this review aims to present an update on the latest studies.
    Matched MeSH terms: Cell Lineage*
  2. Fulltext Platelet rich concentrate promotes early cellular proliferation and multiple lineage differentiation of human mesenchymal stromal cells in vitro
    Shani S, Ahmad RE, Naveen SV, Murali MR, Puvanan K, Abbas AA, et al.
    ScientificWorldJournal, 2014;2014:845293.
    PMID: 25436230 DOI: 10.1155/2014/845293
    Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-γ) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ≤ 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium.
    Matched MeSH terms: Cell Lineage/physiology*
  3. Immunomodulatory Effect of Cytokines in the Differentiation of Mesenchymal Stem Cells: A Review
    Zahari W, Hashim SN, Yusof MF, Osman ZF, Kannan TP, Mokhtar KI, et al.
    Curr Stem Cell Res Ther, 2017;12(3):197-206.
    PMID: 27306400 DOI: 10.2174/1574888X11666160614103404
    Mesenchymal stem cells (MSCs) are stromal origin cells with multilineage differentiation capacity. The immunoregulatory properties of MSCs can be interfered effectively by cytokines. Cytokines, produced by a broad range of cells, act at the systemic level to influence biological phenomena such as inflammation, wound healing, organogenesis and oncogenesis. Cytokines also play vital roles in the differentiation of MSCs into several cell lineages. This review summarizes on how cytokines can affect MSCs differentiation and their relative signaling pathways, which may serve to understand the possible underlying mechanisms. Also, this review reveals the potential clinical use of MSCs as promising therapeutic agents due to their special characteristics such as multipotent differentiation, immunomodulatory properties, and selfrestoration.
    Matched MeSH terms: Cell Lineage/genetics; Cell Lineage/immunology
  4. Effects of Melatonin on Colchicine-Treated PLBs of Dendrobium sonia-28 Orchid
    Lim MS, Antony JJ, Islam SM, Suhana Z, Sreeramanan S
    Appl Biochem Biotechnol, 2017 Jan;181(1):15-31.
    PMID: 27461541 DOI: 10.1007/s12010-016-2196-3
    Dendrobium hybrid orchid is popular in orchid commercial industry due to its short life cycle and ability to produce various types of flower colours. This study was conducted to identify the morphological, biochemical and scanning electron microscopy (SEM) analysis in the Dendrobium sonia-28 orchid plants. In this study, 0.05 and 0.075 % of colchicine-treated Dendrobium sonia-28 (4-week-old culture) protocorm-like bodies (PLBs) were treated in different concentrations of melatonin (MEL) posttreatments (0, 0.05, 0.1, 0.5, 1, 5 and 10 μM). Morphological parameters such as number of shoots, growth index and number of PLBs were determined. In the 0.05 and 0.075 % of colchicine-treated PLBs which were posttreated with 0.05 μM MEL resulted in the highest value of the morphological parameters tested based on the number of shoots (84.5 and 96.67), growth index (16.94 and 12.15) and number of PLBs (126.5 and 162.33), respectively. SEM analysis of the 0.05 μM MEL posttreatment on both the colchicine-treated regenerated PLBs showed irregular cell lineages, and some damages occurred on the stomata. This condition might be due to the effect of plasmolyzing occurred in the cell causing irregular cell lineages.
    Matched MeSH terms: Cell Lineage/drug effects
  5. Notch signaling and ghost cell fate in the calcifying cystic odontogenic tumor
    Siar CH, Kawakami T, Buery RR, Nakano K, Tomida M, Tsujigiwa H, et al.
    Eur J Med Res, 2011 Nov 10;16(11):501-6.
    PMID: 22027644
    Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs) are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites). Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (CCOT), their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4) and three ligands (Jagged1, Jagged2 and Delta1) was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1-Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.
    Matched MeSH terms: Cell Lineage*
  6. Fulltext Misfolded N-CoR is Linked to the Ectopic Reactivation of CD34/Flt3-Based Stem-Cell Phenotype in Promyelocytic and Monocytic Acute Myeloid Leukemia
    Nin DS, Li F, Visvanathan S, Khan M
    Front Oncol, 2015;5:210.
    PMID: 26500885 DOI: 10.3389/fonc.2015.00210
    Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial for the commitment of primitive hematopoietic cells to cells of myeloid lineage and that misfolded N-CoR may contribute to transformation of committed myeloid cells through the ectopic reactivation of Flt3/CD34-based stem cell phenotypes in promyelocytic and monocytic AML. Moreover, these findings provide novel mechanistic insights into the formation of leukemic stem cells in subsets of AML and identify the misfolded N-CoR as a subtype-specific biomarker of AML.
    Matched MeSH terms: Cell Lineage
  7. The design of a thermoresponsive surface for the continuous culture of human pluripotent stem cells
    Sung TC, Yang JS, Yeh CC, Liu YC, Jiang YP, Lu MW, et al.
    Biomaterials, 2019 Nov;221:119411.
    PMID: 31419657 DOI: 10.1016/j.biomaterials.2019.119411
    Commonly, stem cell culture is based on batch-type culture, which is laborious and expensive. We continuously cultured human pluripotent stem cells (hPSCs) on thermoresponsive dish surfaces, where hPSCs were partially detached on the same thermoresponsive dish by decreasing the temperature of the thermoresponsive dish to be below the lower critical solution temperature for only 30 min. Then, the remaining cells were continuously cultured in fresh culture medium, and the detached stem cells were harvested in the exchanged culture medium. hPSCs were continuously cultured for ten cycles on the thermoresponsive dish surface, which was prepared by coating the surface with poly(N-isopropylacrylamide-co-styrene) and oligovitronectin-grafted poly(acrylic acid-co-styrene) or recombinant vitronectin for hPSC binding sites to maintain hPSC pluripotency. After ten cycles of continuous culture on the thermoresponsive dish surface, the detached cells expressed pluripotency proteins and had the ability to differentiate into cells derived from the three germ layers in vitro and in vivo. Furthermore, the detached cells differentiated into specific cell lineages, such as cardiomyocytes, with high efficiency.
    Matched MeSH terms: Cell Lineage
  8. Microenvironmental factors involved in human amnion mesenchymal stem cells fate decisions
    Syva SH, Ampon K, Lasimbang H, Fatimah SS
    J Tissue Eng Regen Med, 2017 02;11(2):311-320.
    PMID: 26073746 DOI: 10.1002/term.2043
    Human amnion mesenchymal stem cells (HAMCs) show great differentiation and proliferation potential and also other remarkable features that could serve as an outstanding alternative source of stem cells in regenerative medicine. Recent reports have demonstrated various kinds of effective artificial niche that mimic the microenvironment of different types of stem cell to maintain and control their fate and function. The components of the stem cell microenvironment consist mainly of soluble and insoluble factors responsible for regulating stem cell differentiation and self-renewal. Extensive studies have been made on regulating HAMCs differentiation into specific phenotypes; however, the understanding of relevant factors in directing stem cell fate decisions in HAMCs remain underexplored. In this review, we have therefore identified soluble and insoluble factors, including mechanical stimuli and cues from the other supporting cells that are involved in directing HAMCs fate decisions. In order to strengthen the significance of understanding on the relevant factors involved in stem cell fate decisions, recent technologies developed to specifically mimic the microenvironments of specific cell lineages are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd.
    Matched MeSH terms: Cell Lineage*
  9. Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy
    Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
    Matched MeSH terms: Cell Lineage*
  10. Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells
    Chow PW, Abdul Hamid Z, Chan KM, Inayat-Hussain SH, Rajab NF
    Toxicol Appl Pharmacol, 2015 Apr 1;284(1):8-15.
    PMID: 25645895 DOI: 10.1016/j.taap.2015.01.016
    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e(+) cells but reduced the total counts of Sca-1(+), CD11b(+), Gr-1(+), and CD45(+) cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage.
    Matched MeSH terms: Cell Lineage*
  11. A plethora of human pluripotent stem cells
    Gao L, Thilakavathy K, Nordin N
    Cell Biol Int, 2013 Sep;37(9):875-87.
    PMID: 23619972 DOI: 10.1002/cbin.10120
    At the early stages of mammalian development, a number of developmentally plastic cells appear that possess the ability to give rise to all of the differentiated cell types normally derived from the three primary germ layers - unique character known as pluripotency. To date, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to be truly pluripotent. However, recent studies have revealed a variety of other cells that demonstrate pluripotentiality, including very small embryonic-like stem cells (VSELs), amniotic fluid stem cells (AFSCs), marrow-isolated adult multilineage inducible cells (MIAMI) and multipotent adult precursor cells (MAPCs). This review summarises key features of these six kinds of pluripotent and potentially pluripotent stem cells (ESCs, iPSCs, VSELs, AFSCs, MIAMI and MAPCs) and the evidence for their pluripotency properties.
    Matched MeSH terms: Cell Lineage/genetics
  12. Fulltext Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype
    Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, et al.
    J Biomed Sci, 2018 Jul 19;25(1):57.
    PMID: 30025541 DOI: 10.1186/s12929-018-0461-1
    BACKGROUND: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

    METHODS: iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis.

    RESULTS: The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation.

    CONCLUSIONS: Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

    Matched MeSH terms: Cell Lineage/genetics
  13. The mechanisms of fibroblast-mediated compaction of collagen gels and the mechanical niche around individual fibroblasts
    Feng Z, Wagatsuma Y, Kikuchi M, Kosawada T, Nakamura T, Sato D, et al.
    Biomaterials, 2014 Sep;35(28):8078-91.
    PMID: 24976242 DOI: 10.1016/j.biomaterials.2014.05.072
    Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo.
    Matched MeSH terms: Cell Lineage
  14. Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung Cancer (A549) Cell Line
    Halim NHA, Zakaria N, Satar NA, Yahaya BH
    Methods Mol Biol, 2016;1516:371-388.
    PMID: 27032945 DOI: 10.1007/7651_2016_326
    Cancer is a major health problem worldwide. The failure of current treatments to completely eradicate cancer cells often leads to cancer recurrence and dissemination. Studies have suggested that tumor growth and spread are driven by a minority of cancer cells that exhibit characteristics similar to those of normal stem cells, thus these cells are called cancer stem cells (CSCs). CSCs are believed to play an important role in initiating and promoting cancer. CSCs are resistant to currently available cancer therapies, and understanding the mechanisms that control the growth of CSCs might have great implications for cancer therapy. Cancer cells are consist of heterogeneous population of cells, thus methods of identification, isolation, and characterisation of CSCs are fundamental to obtain a pure CSC populations. Therefore, this chapter describes in detail a method for isolating and characterizing a pure population of CSCs from heterogeneous population of cancer cells and CSCs based on specific cell surface markers.
    Matched MeSH terms: Cell Lineage
  15. Fulltext Correlation between corresponding protein and MRNA in acute myeloid leukaemia (AML)
    Siti Zuleha Idris, Stephnie Yiau Kang Xian, Lee CinDee, Eusni Rahayu Mohd. Tohit, Chang Kian Meng, Maha Abdullah
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):43-43.
    MyJurnal
    Introduction: Protein and gene expressions are intensively profiled for potential biomarkers in diagnosis or prognosis of diseases. The correlation between corresponding protein and mRNA of a gene is important to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. mRNA profiling is more commonly utilised as this method is cheaper and the technology more advanced. Acute myeloid leukaemia (AML) is a heterogeneous group of malignant precursors of the myeloid lineage that leads to death if not treated. Cytokines and death receptors are commonly evaluated in this disease in search of potential biomarkers; however, the mRNA/protein correlations of these biomarkers are still unclear. Methods: Semi-quantitative expression of mRNA expression and protein levels of IL-1β, IL-18Rα, IL-6, TNF-α and DR5 were measured by conventional polymerase reaction (PCR) and flow cytometry in 11 cases of AML at diagnosis. Correlation in the intensity of the PCR amplicon and corre-sponding mean fluorescence intensity of protein was determined by Spearman’s rank correlation test. Results: None of the cytokines/death receptor was significantly correlated except IL-6 (Rs= -0.6287, p=0.038). Unexpectedly, this was also a significant negative correlation. Conclusion: For the majority of selected biomarkers in AML, whether secreted or surface-expressed, mRNA and protein expressions were not significantly correlated. The strong negative correlation for IL-6 is worth further investigation.
    Matched MeSH terms: Cell Lineage
  16. Xeno-free and feeder-free culture and differentiation of human embryonic stem cells on recombinant vitronectin-grafted hydrogels
    Chen LH, Sung TC, Lee HH, Higuchi A, Su HC, Lin KJ, et al.
    Biomater Sci, 2019 Aug 14.
    PMID: 31411209 DOI: 10.1039/c9bm00418a
    Recombinant vitronectin-grafted hydrogels were developed by adjusting surface charge of the hydrogels with grafting of poly-l-lysine for optimal culture of human embryonic stem cells (hESCs) under xeno- and feeder-free culture conditions, with elasticity regulated by crosslinking time (10-30 kPa), in contrast to conventional recombinant vitronectin coating dishes, which have a fixed stiff surface (3 GPa). hESCs proliferated on the hydrogels for over 10 passages and differentiated into the cells derived from three germ layers indicating the maintenance of pluripotency. hESCs on the hydrogels differentiated into cardiomyocytes under xeno-free culture conditions with much higher efficiency (80% of cTnT+ cells) than those on conventional recombinant vitronectin or Matrigel-coating dishes just only after 12 days of induction. It is important to have an optimal design of cell culture biomaterials where biological cues (recombinant vitronectin) and physical cues (optimal elasticity) are combined for high differentiation of hESCs into specific cell lineages, such as cardiomyocytes, under xeno-free and feeder-free culture conditions.
    Matched MeSH terms: Cell Lineage
  17. Fulltext MicroRNA-124a inhibits endoderm lineage commitment by targeting Sox17 and Gata6 in mouse embryonic stem cells
    Liew LC, Gailhouste L, Tan GC, Yamamoto Y, Takeshita F, Nakagama H, et al.
    Stem Cells, 2020 04;38(4):504-515.
    PMID: 31828873 DOI: 10.1002/stem.3136
    The role of microRNAs (miRNAs) during mouse early development, especially in endoderm germ layer formation, is largely unknown. Here, via miRNA profiling during endoderm differentiation, we discovered that miR-124a negatively regulates endoderm lineage commitment in mouse embryonic stem cells (mESCs). To further investigate the functional role of miR-124a in early stages of differentiation, transfection of embryoid bodies with miR-124a mimic was performed. We showed that overexpression of miR-124a inhibits endoderm differentiation in vitro through targeting the 3'-untranslated region (UTR) of Sox17 and Gata6, revealing the existence of interplay between miR-124a and the Sox17/Gata6 transcription factors in hepato-specific gene regulation. In addition, we presented a feasible in vivo system that utilizes teratoma and gene expression profiling from microarray to quantitatively evaluate the functional role of miRNA in lineage specification. We demonstrated that ectopic expression of miR-124a in teratomas by intratumor delivery of miR-124a mimic and Atelocollagen, significantly suppressed endoderm and mesoderm lineage differentiation while augmenting the differentiation into ectoderm lineage. Collectively, our findings suggest that miR-124a plays a significant role in mESCs lineage commitment.
    Matched MeSH terms: Cell Lineage
  18. Cutaneous involvement of multiple myeloma
    Mohtarrudin N, Bakrin IH, Ambrose D, Jo Lyn L, Mukhtar NSA
    Malays J Pathol, 2021 Apr;43(1):75-79.
    PMID: 33903309
    Cutaneous multiple myeloma (MM) is a rare disease. It can be primary or secondary in origin. The secondary type is further classified into specific and nonspecific types. The specific type is uncommon and is known as a secondary cutaneous plasmacytoma. We report a case of secondary cutaneous plasmacytoma in a 58-year-old man who had a history of plasma cell tumour of the lung and multiple myeloma. He achieved complete remission after the completion of chemotherapy and autologous stem cell transplant (ASCT). However, five months later, he developed multiple erythematous nodules on the whole body. Skin biopsy revealed diffuse neoplastic cells infiltrate in the reticular dermis with sparing of the upper papillary dermis and epidermis. The neoplastic cells were monotonous and homogenous with variable degrees of cytological atypia. Occasional cells showed distinctive plasma cell features. Plasma cell lineage was confirmed with CD138. The cells were immunoreactive to Kappa. Ki-67 was greater than 90%. They were non-immunoreactive to CD45, CD3, CD20, CD79 alpha and CK AE1/AE3. The findings were consistent with secondary cutaneous plasmacytoma. Our case illustrates that MM may present with nonspecific dermatological manifestations. As specific cutaneous involvement of MM is very uncommon; a high degree of clinical suspicion, detailed medical history and histopathological examination are required to arrive at an early diagnosis.
    Matched MeSH terms: Cell Lineage
  19. Expansion of Hydra actinoporin-like toxin (HALT) gene family: Expression divergence and functional convergence evolved through gene duplication
    Yap WY, Tan KJSX, Hwang JS
    Toxicon, 2019 Dec;170:10-20.
    PMID: 31513812 DOI: 10.1016/j.toxicon.2019.09.007
    Hydra actinoporin-like toxin 1 (HALT-1) was previously shown to cause cytolysis and haemolysis in a number of human cells and has similar functional properties to the actinoporins equinatoxin and sticholysin. In addition to HALT-1, five other HALTs (HALTs 2, 3, 4, 6 and 7) were also isolated from Hydra magnipapillata and expressed as recombinant proteins in this study. We demonstrated that recombinant HALTs have cytolytic activity on HeLa cells but each exhibited a different range of toxicity. All six recombinant HALTs bound to sulfatide, while rHALT-1 and rHALT-3 bound to two additional sphingolipids, lysophosphatidic acid and sphingosine-1-phosphate as indicated by the protein-lipid overlay assay. When either tryptophan133 or tyrosine129 of HALT-1 was mutated, the mutant protein lost binding to sulfatide, lysophosphatidic acid and sphingosine-1-phosphate. As further verification of HALTs' binding to sulfatide, we performed ELISA for each HALT. To determine the cell-type specific gene expression of seven HALTs in Hydra, we searched for individual HALT expression in the single-cell RNA-seq data set of Single Cell Portal. The results showed that HALT-1, 4 and 7 were expressed in differentiating stenoteles. HALT-1 and HALT-6 were expressed in the female germline during oogenesis. HALT-2 was strongly expressed in the gland and mucous cells in the endoderm. Information on HALT-3 and HALT-5 could not be found in the single-cell data set. Our findings show that subfunctionalisation of gene expression following duplication enabled HALTs to become specialized in various cell types of the interstitial cell lineage.
    Matched MeSH terms: Cell Lineage
  20. Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development
    Yang C, Li X, Li Q, Li H, Qiao L, Guo Z, et al.
    J Mol Neurosci, 2018 Feb;64(2):287-299.
    PMID: 29285739 DOI: 10.1007/s12031-017-1019-5
    During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development. Here, we aimed at studying how Shh might regulate chicken optic tectum patterning. In the present study, in ovo electroporation methods were employed to achieve the overexpression of Shh in the optic tectum during chicken embryo development. Besides, the study combined in ovo electroporation and neuron isolation culturing to study the function of Shh in vivo and in vitro. The fluorescent immunohistochemistry methods were used to check the related indicators. The results showed that Shh overexpression caused 87.8% of cells to be distributed to the stratum griseum central (SGC) layer, while only 39.3% of the GFP-transfected cells resided in the SGC layer in the control group. Shh overexpression also reduced the axon length in vivo and in vitro. In conclusion, we provide evidence that Shh regulates the neural precursor cell fate during chicken optic tectum development. Shh overexpression impairs neuronal migration and may affect the fate determination of transfected neurons.
    Matched MeSH terms: Cell Lineage
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