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Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominindae-Specific Viral Infections [ChIP-seq]

ABSTRACT: Here, we report the genomic binding profile of NANOG and SOX17 in human embryonic stem cells and human primordial germ cell-like cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182216 | GEO | 2021/11/09

REPOSITORIES: GEO

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Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominindae-Specific Viral Infections [RNA-seq]

Project description:Here, we report the transcriptome profile for dCAS9-KRAB CRISPRi targeting LTR5Hs in human primordial germ cell-like cells.

2021-11-09 | GSE182217 | GEO

Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominidae-Specific Viral Infections

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-07 | GSE182218 | GEO

Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominidae-Specific Viral Infections

Project description:Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominidae-Specific Viral Infections

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Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominindae-Specific Viral Infections [RNA-seq]

Project description:Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominindae-Specific Viral Infections [RNA-seq]

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Human Reproduction is Regulated by Retrotransposons derived from Ancient Hominindae-Specific Viral Infections [ChIP-seq]

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GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program [Bisulfite-Seq]

Project description:The in vitro reconstitution of human germ-cell development provides a robust framework for clarifying key underlying mechanisms. Here, we explored transcription factors (TFs) that engender the germ-cell fate in their pluripotent precursors. Unexpectedly, SOX17, TFAP2C, and BLIMP1, which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, GATA3 or GATA2, immediate BMP effectors, combined with SOX17 and TFAP2C, generated hPGCLCs. GATA3/GATA2 knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas GATA3/GATA2 expression remained unaffected in SOX17, TFAP2C, or BLIMP1 knockouts. In cynomolgus monkeys, a key model for human development, GATA3, SOX17, and TFAP2C were co-expressed exclusively in early PGCs. Crucially, the TF-induced hPGCLCs acquired a hallmark of bona fide hPGCs to undergo epigenetic reprogramming and mature into oogonia/gonocytes in xenogeneic reconstituted ovaries. By uncovering a TF circuitry driving the germ line program, our study provides a paradigm for TF-based human gametogenesis.

2021-02-16 | GSE154690 | GEO

GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program [RNA-Seq]

2021-02-16 | GSE154688 | GEO

GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program

2021-02-15 | GSE154691 | GEO

A Signaling and Transcription Architecture for the Specification of Human Germ Cell Lineage

Project description:The mechanism for human germ-cell specification, which sets out a complex program generating spermatozoa or oocytes, remains largely unknown. We established a system for inducing human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) via incipient mesoderm-like cells (iMeLCs). Here, we show that EOMESODERMIN (EOMES) elevates in iMeLCs through WNT signaling and is essential for activating SOX17, a key driver for hPGC(LC) specification, with the duration/dosage of the WNT signaling/EOMES expression dictating the germ-cell competence. Upon hPGCLC induction, BMP signaling activates TFAP2C independently from SOX17, and SOX17 and TFAP2C instate the hPGCLC program, including BLIMP1 expression, in an interdependent fashion. The hPGC(LC) specification program is highly consistent with the monkey program, but is divergent from the mouse one regarding key transcription factors and their hierarchy of actions. These findings delineate evolutionary divergence of mammalian germ-cell specification, providing a foundation for further human germ-cell development in vitro.

2018-02-21 | GSE99350 | GEO

Sequential enhancer state remodelling defines human germline competence and specification [RNAseq_WildType]

Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.

2022-01-24 | GSE159653 | GEO

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