The transcriptional regulation of pluripotency

Yeo, Jia-Chi; Ng, Huck Hui

doi:10.1038/cr.2012.172

Cited by 117 publications

(88 citation statements)

References 148 publications

(212 reference statements)

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“…[5][6][7][8] Gene expression in ESCs is regulated by a complex network of transcription factors. 9,10 In addition, numerous results indicate that miRNAs are crucial regulators of the gene expression programs that drive ESC differentiation. Suppression of miRNA biogenesis, obtained by knocking out Dicer or DCGR8 genes, leads to an early arrest of mouse embryonic development and of in vitro differentiation of ESCs.…”

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confidence: 99%

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

et al. 2014

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Numerous studies have indicated that BMP4 signaling is involved in the regulation of the early steps of development. In mouse embryonic stem cells (ESCs), BMP4 is crucial to sustain pluripotency and blocks differentiation towards neural fate. Here, through a systematic analysis of miRNAs in ESCs, we establish that BMP4 signaling regulates miR-23a, 27a and 24-2, through the recruitment of phospho-Smads at the promoter of the gene encoding this miRNA cluster. Suppression of miR-23a/b, 27a/b and 24 does not affect self-renewal or pluripotency, but induces an evident change of ESC differentiation, with a significant increase of the cells undergoing apoptosis after the transition from ESCs to epiblast stem cells (EpiSCs). BMP4 has been previously reported to cause apoptosis during ESC differentiation. By blocking BMP4 signaling, we completely prevent the apoptosis induced by suppression of the miRs. This suggests that the effects of miR suppression are the result of enhanced BMP4 signaling. This hypothesis is further supported by the observation that Smad5, the transcription factor downstream of the BMP4 receptor, is targeted by the miRNAs of the 23a and 23b clusters. Altogether, our results highlight the existence of a regulatory loop, involving Smad5 and the miR-23a clusters, that modulates the apoptotic response of ESCs to BMP4. Cell Death and Differentiation (2015) 22, 1047-1057 doi:10.1038/cdd.2014; published online 5 December 2014ESCs represent a precious experimental model of the early stages of embryo development. They can be grown indefinitely in vitro and induced to differentiate, thus mimicking two events taking place in the blastocyst: (i) the differentiation of the cells of the inner cell mass into epiblast cells and (ii) the commitment of epiblast cells to neuroectodermal or mesendodermal precursors. 1,2 These differentiation events are regulated by extrinsic signals. BMP4, a member of the TGF-β superfamily of cytokines, has a crucial role in ESCs. Many results indicate that it is able, together with LIF, to maintain mouse ESCs in the pluripotent state. 3 This effect is mediated by the regulation of many direct targets of Smad1, 5 and 8, the transcription factors downstream of the BMP4 receptor. 4 BMP4 also contributes to govern early steps of differentiation. First, BMP4 acts by regulating ESC-epiblast transition and then by suppressing neural differentiation and promoting non-neural lineage formation. 2 Moreover, BMP4 promotes the differentiation towards mesendodermal lineages and also regulates, either positively or negatively, the further commitment of mesendodermal precursors into their different fates. [5][6][7][8] Gene expression in ESCs is regulated by a complex network of transcription factors. 9,10 In addition, numerous results indicate that miRNAs are crucial regulators of the gene expression programs that drive ESC differentiation. Suppression of miRNA biogenesis, obtained by knocking out Dicer or DCGR8 genes, leads to an early arrest of mouse embryonic development and of in vitro differenti...

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confidence: 99%

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

et al. 2014

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“…The SC have been reported in different adult organs on the basis of their capacity to proliferate and carry out self-renewal, a differentiation potential, and the ability to regenerate tissue after cell loss and are able to express key marker genes (32,35,41), with the principal ones being the transcription factors Oct-4 and Sox2, which are involved in the maintenance of pluripotency in the genome of SC (48,55). The Sox9 progenitor marker, a member of the SoxE subfamily, is important in embryonic and postnatal development (9) and participates in differentiation programs by activation of tissue-specific genes (26).…”

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confidence: 99%

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Vaca

Guido

Sosa

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.

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“…Genes characterized for pluripotency control are predominantly composed of transcription factors, thus pluripotency-associated transcription factors (PATF) (Young, 2011;Yeo and Ng, 2013). These PATFs act on gene regulation, by inducing or silencing target genes.…”

Section: Pluripotency-associated Transcription Factorsmentioning

confidence: 99%

Lessons learned from functional assessment of pluripotency-associated transcription factors during early embryogenesis and embryonic stem cells

et al. 2017

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Pluripotency-associated transcription factors (PATF) play significant roles during early embryogenesis and in embryonic stem (ES) cells, such as control of cell-cycle progression, modulation of cellular metabolism, and transcriptional control of differentiation-inducing factors. The review aims to describe the current understanding of how these PATFs contribute to the early embryo and the ES-cell phenotypes. By a selection of representative examples of such PATFs, their roles are described, and some interesting questions are presented concerning their activity in pluripotent cells which have yet to be addressed.Keywords: embryology; pluripotent; preimplantation development; totipotency. ResumoFatores de transcrição relacionados à pluripotência (FTRP) apresentam importantes funções durante a embriogênese inicial e em células-tronco embrionárias (CTE), como o controle da progressão do ciclo celular, modulação do metabolismo celular e controle transcricional de fatores indutores de diferenciação celular. O objetivo da revisão foi descrever o conhecimento vigente sobre como estes FTRPs contribuem para o fenótipo dos embriões e CTEs. Através da seleção de exemplos representativos destes FTRPs, suas funções são descritas e algumas perguntas interessantes são apresentadas considerando suas atividades em células pluripotentes, mas que ainda não foram devidamente respondidas.Palavras-Chave: embriologia; pluripotente; desenvolvimento pré-implantacional; totipotência.

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The transcriptional regulation of pluripotency

Cited by 117 publications

References 148 publications

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Lessons learned from functional assessment of pluripotency-associated transcription factors during early embryogenesis and embryonic stem cells

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