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The catalytic activity of TET1 is required for human germ cell fate choice [scRNA-seq]

ABSTRACT: Primordial germ cell (PGC) is the foundation of the germline which become gametes and transmit genetic and epigenetic information to the next generation. The segregation of germline and soma is critical yet well-characterized in human during embryonic development due to ethical consideration. Here we discover that human TET1 (Ten-eleven translocation 1) acts as a safety check of germline cell fate. Using CRISPR/Cas9 to knock-out TET1 catalytic domain, we demonstrate extremely low hPGCLC (hPGC-like cell) competency of undifferentiated pluripotent stem cell lines. We plot whole-genome 5’hydroxymethylation (5hmC) profiles to elucidate global as well as locus-specific 5hmC enrichment in hPGCLCs, indicating the DNA oxygenase activity of TET1 is active during hPGCLC differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217542 | GEO | 2023/09/12

REPOSITORIES: GEO

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The catalytic activity of TET1 is required for human germ cell fate choice [bACE-Seq]

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SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

Project description:Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information. RNA-Seq analysis to investigate transcriptomes of hPGC-like cells (hPGCLCs), fetal hPGCs, TCam-2 and hESCs

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2022-04-30 | GSE148717 | GEO

The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation

Project description:Human primordial germ cells (hPGCs) are the first embryonic progenitors in the germ cell lineage, yet the molecular mechanisms required for hPGC formation are not well characterized. To identify regulatory regions in hPGC development, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to systematically characterize regions of open chromatin in hPGCs and hPGC-like cells (hPGCLCs) differentiated from human embryonic stem cells (hESCs). We discovered regions of open chromatin unique to hPGCs and hPGCLCs that significantly overlap with TFAP2C-bound enhancers identified in the naive ground state of pluripotency. Using CRISPR/Cas9, we show that deleting the TFAP2C-bound naive enhancer at the OCT4 locus (also called POU5F1) results in impaired OCT4 expression and a negative effect on hPGCLC identity.

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Specification of human germ cell fate with enhanced progression capability

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