Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 6 Articles
Cellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic\nstem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels.\nSeveral studies have indicated that the stochastic activation of signaling networks may promote heterogeneity and further that this\nheterogeneity may be reduced by their inhibition. But why different cells in the same culture respond in a nonuniform manner to\nthe identical exogenous signals has remained unclear. Recent studies nowdemonstrate that the cell cycle position directly influences\nlineage specification and specifically that pluripotent stem cells initiate their differentiation fromtheG1 phase. These studies suggest\nthat cells in G1 are uniquely ââ?¬Å?poisedââ?¬Â to undergo cell specification. G1 cells are therefore more prone to respond to differentiation\ncues, which may explain the heterogeneity of developmental factors, such as Gata6, and pluripotency factors, such as Nanog, in\nstem cell cultures. Overall, this raises the possibility that G1 serves as a ââ?¬Å?Differentiation Induction Point.ââ?¬Â In this review, we will\nreexamine the literature describing heterogeneity of pluripotent stem cells, while highlighting the role of the cell cycle as a major\ndeterminant...
Following the discovery of pluripotent stem (PS) cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells, there\nhas been a great hope that injured tissues can be repaired by transplantation of ES/iPS-derived various specific types of cells such\nas neural stem cells (NSCs). Although PS cells can be induced by ectopic expression of Yamanaka�s factors, it is known that several\nstimuli such as ischemia/hypoxia can increase the stemness of somatic cells via reprogramming. This suggests that endogenous\nsomatic cells acquire stemness during natural regenerative processes following injury. In this study, we describe whether somatic\ncells are converted into pluripotent stem cells by pathological stimuli without ectopic expression of reprogramming factors based\non the findings of ischemia-induced multipotent stem cells in a mouse model of cerebral infarction....
Induced pluripotent stem cells (iPSCs) are generated through a gradual process in which somatic cells undergo a number of\nstochastic events. In this study, we examined whether two different doxycycline-inducible iPSCs, slow-forming 4F2A-iPSCs and\nfast-forming NGFP-iPSCs, have equivalent levels of pluripotency. Multiplex reverse-transcriptase PCR generated gene expression\nprofiles (GEPs) of 13 pluripotency genes in single initially formed-iPSC (if-iPSC) colonies of NGFP and 4F2A group. Assessment\nof GEP difference using a weighted root mean square deviation (wRMSD) indicates that 4F2A if-iPSCs are more closely related\nto mESCs than NGFP if-iPSCs. Consistently, Nanog and Sox2 genes were more frequently derepressed in 4F2A if-iPSC group.We\nfurther examined 20 genes that are implicated in reprogramming. They were, overall, more highly expressed in NGFP if-iPSCs,\ndiffering from the pluripotency genes being more expressed in 4F2A if-iPSCs. wRMSD analysis for these reprogramming-related\ngenes confirmed that the 4F2A if-iPSC colonies were less deviated from mESCs than the NGFP if-iPSC colonies. Our findings\nsuggest that more important in attaining a better reprogramming is the mode of action by the given reprogramming factors, rather\nthan the total activity of them exerting to the cells, as the thin-but-long-lasting mode of action in 4F2A if-iPSCs is shown to be\nmore effective than its full-but-short-lasting mode in NGFP if-iPSCs....
Activation ofWnt signaling enhances self-renewal of mouse embryonic and neural stem/progenitor cells. In contrast, undifferentiated\nES cells show a very low level of endogenousWnt signaling, and ectopic activation ofWnt signaling has been shown to block\nneuronal differentiation. Therefore, it remains unclear whether or not endogenous Wnt/????-catenin signaling is necessary for selfrenewal\nor neuronal differentiation of ES cells.To investigate this,we examined the expression profiles ofWnt signaling components.\nExpression levels of Wnts known to induce ????-catenin were very low in undifferentiated ES cells. Stable ES cell lines which can\nmonitor endogenous activity of Wnt/????-catenin signaling suggest that Wnt signaling was very low in undifferentiated ES cells,\nwhereas it increased during embryonic body formation or neuronal differentiation. Interestingly, application of small molecules\nwhich can positively (BIO, GSK3???? inhibitor) or negatively (IWR-1-endo, Axin stabilizer) controlWnt/????-catenin signaling suggests\nthat activation of that signaling at different time periods had differential effects on neuronal differentiation of 46C ES cells. Further,\nChIP analysis suggested that ????-catenin/TCF1 complex directly regulated the expression of Sox1 during neuronal differentiation.\nOverall, our data suggest thatWnt/????-catenin signaling plays differential roles at different time points of neuronal differentiation....
Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular\nendothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further\ninvestigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression\nof integrins ????1????1 and ????5????1, which are known to mediate physiological and pathological angiogenesis. Our results showed that\nincreased expression of ????1, ????5, and ????1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling\npathwaywas demonstrated to be involved in regulating the expression of integrins ????1, ????5, and ????1. Luciferase reporter assay andChIP\nassay determined that MRTF-A could bind to and transactivate the integrin ????1 and ????5 promoters. Treatment with the Rho inhibitor\nC3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation\nof ????1, ????5, and ????1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion\nled to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate\nthat Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic\nprocesses....
We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to\ndifferent cryopreservation lengths (2ââ?¬â??1159 days) from patients of varying ages (26ââ?¬â??62 years). Subcutaneous abdominal adipose\ntissue was excised during abdominoplasties and was cryopreserved.The viability and number of adipose-derived stem cells isolated\nwere measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation\nduration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved <1 year than from tissue\ncryopreserved >2 years, irrespective of patient age. However, this difference did not persist with continued growth and there were\nno significant differences in cell viability or growth at subsequent time points with respect to cryopreservation duration or patient\nage. Mesenchymal stem cell markers were maintained in all cohorts tested throughout the duration of the study. Consequently,\nlonger cryopreservation negatively impacts initial live adipose-derived stem cell isolation; however, this effect is neutralized with\ncontinued cell growth. Patient age does not significantly impact stemcell isolation, viability, or growth. Cryopreservation of adipose\ntissue is an effective long-term banking method for isolation of adipose-derived stem cells in patients of varying ages....
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