The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells

Veerapandian, Veeramohan; Yang, Xinyan; Song, Ke; Xu, Xiaofei; Cui, Manman; Yuan, Weiyan; Huang, Yaping; Xia, Xinyu; Yao, Zhaokai; Wan, Cong; Luo, Fang; Song, Xiuling; Wang, Xiaoru; Zheng, Yi; Hutchins, Andrew P.; Jauch, Ralf; Wang, Chenhong; Liu, Zhaoting; Chang, Gang; Zhao, Xiaoyang

doi:10.1016/j.stemcr.2021.03.032

Cited by 19 publications

(7 citation statements)

References 38 publications

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“…It is known that several key primordial germ cell (PGC) TFs including PRDM14 promote iPSC generation (70, 98–100). Coupled with recent reports implicating a role of SOX15 in PGC fate specification (101, 102) and our observation that Prdm14 is downregulated in Sox15 KO ESCs, we speculate that SOX15 may regulate reprogramming by promoting the expression of critical PGC-associated TFs. It is also possible that SOX15, together with SOX2, ensures optimal reactivation of the pluripotency gene network during reprogramming.…”

Section: Discussionsupporting

confidence: 88%

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

Choi

Saini

Zerbato

et al. 2022

Preprint

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SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 largely because overexpression of SOX15 can partially restore self-renewal in SOX2-deficient ESCs. Here, we show that SOX15 contributes to stem cell maintenance by cooperating with ESC-enriched transcriptional coactivators to ensure optimal expression of pluripotency-associated genes. We demonstrate that SOX15 depletion compromises reprogramming of fibroblasts to pluripotency which cannot be compensated by SOX2. Ectopic expression of SOX15 promotes the reversion of a post-implantation, epiblast stem cell state back to a pre-implantation, ESC-like identity even though SOX2 is expressed in both cell states. We also uncover a role of SOX15 in lineage specification, by showing that loss of SOX15 leads to defects in commitment of ESCs to neural fates. SOX15 promotes neural differentiation by binding to and activating a previously uncharacterized distal enhancer of a key neurogenic regulator, Hes5. Together, these findings identify a multifaceted role of SOX15 in induction and maintenance of pluripotency and neural differentiation.

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Section: Discussionsupporting

confidence: 88%

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

Choi

Saini

Zerbato

et al. 2022

Preprint

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“…The CUT&Tag method, which involves fusing protein A/G with the Tn5 transposition enzyme, is a novel approach for investigating the interaction between proteins and DNA (Tao et al., 2020; Wang et al., 2021). Through the utilization of the CUT&Tag assay and the dual luciferase assay, we were able to confirm a direct correlation between miR‐27a‐5p and NF‐κB1.…”

Section: Discussionmentioning

confidence: 99%

NF‐κB1 promotes miR‐27a‐5p upregulation in acrylamide‐induced toxicity in rats

Zhang,

Yang,

Gao

et al. 2024

Food Frontiers

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Acrylamide (AA) is a neurotoxic and potentially carcinogenic contaminant, usually generated during food processing. MicroRNAs are a class of noncoding small RNAs, which serve essential pathogenic roles in linking exposure to toxic contaminants with their pathological outcomes. Our previous research identified miR‐27a‐5p as a key regulator in AA toxicity, as it induces mitochondria‐dependent apoptosis by targeting Btf3 in rats. However, the mechanisms by which miR‐27a‐5p is regulated to exert its toxic effects remain unclear. Here, the transcription factors that bind to the promoter of miR‐27a‐5p and their potential regulatory functions are investigated in cell lines and rats. The results showed that nuclear factor kappa‐B 1 (NF‐κB1) is a promising transcription factor from bioinformatic analysis. The luciferase reporter assay demonstrated that NF‐κB1 enhances the transcriptional activity of the miR‐27a‐5p promoter, whereas the cleavage under targets and tagmentation assay successfully verified the specific binding sites at −305/−298 bp. Furthermore, the inhibition of NF‐κB1 resulted in the suppression of miR‐27a‐5p expression and its associated target pathways, with additional validation provided by in vivo experimentation. Consequently, the upregulation of miR‐27a‐5p induced by AA and its subsequent intrinsic apoptosis can be attributed to the binding of NF‐κB1 to the miR‐27a‐5p promoter. This binding event may serve as the initial step in the molecular network regulated by miR‐27a‐5p that underlies AA toxicity.

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“…Undifferentiated pluripotent cells are characterized by spherical nuclei with predominantly euchromatic features [12]. Similarly, stem cells have fewer heterochromatin foci and are less organized than differentiated cells [13,14], showing that pluripotent cells are more euchromatic and allow transcription factor access to genes for multiple lineages [15]. This pattern is also observed in early embryos, where the nucleus is largely euchromatic and develops structural landmarks during gastrulation and somitogenesis [11,16,17].…”

Section: Introductionmentioning

confidence: 88%

Nuclear Organization during Hepatogenesis in Zebrafish Requires Uhrf1

Madakashira

Zhang

Macchi

et al. 2021

Genes

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Acquisition of cellular fate during development is initiated and maintained by well-coordinated patterns of gene expression that are dictated by the epigenetic landscape and genome organization in the nucleus. While the epigenetic marks that mediate developmental gene expression patterns during organogenesis have been well studied, less is known about how epigenetic marks influence nuclear organization during development. This study examines the relationship between nuclear structure, chromatin accessibility, DNA methylation, and gene expression during hepatic outgrowth in zebrafish larvae. We investigate the relationship between these features using mutants that lack DNA methylation. Hepatocyte nuclear morphology was established coincident with hepatocyte differentiation at 80 h post-fertilization (hpf), and nuclear shape and size continued to change until the conclusion of outgrowth and morphogenesis at 120 hpf. Integrating ATAC-Seq analysis with DNA methylation profiling of zebrafish livers at 120 hpf showed that closed and highly methylated chromatin occupies most transposable elements and that open chromatin correlated with gene expression. DNA hypomethylation, due to mutation of genes encoding ubiquitin-like, containing PHD and RING Finger Domains 1 (uhrf1) and DNA methyltransferase (dnmt1), did not block hepatocyte differentiation, but had dramatic effects on nuclear organization. Hepatocytes in uhrf1 mutants have large, deformed nuclei with multiple nucleoli, downregulation of nucleolar genes, and a complete lack of the nuclear lamina. Loss of lamin B2 staining was phenocopied by dnmt1 mutation. Together, these data show that hepatocyte nuclear morphogenesis coincides with organ morphogenesis and outgrowth, and that DNA methylation directs chromatin organization, and, in turn, hepatocyte nuclear shape and size during liver development.

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The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells

Cited by 19 publications

References 38 publications

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

NF‐κB1 promotes miR‐27a‐5p upregulation in acrylamide‐induced toxicity in rats

Nuclear Organization during Hepatogenesis in Zebrafish Requires Uhrf1

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