The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE169577 | GEO | 2021/04/07
REPOSITORIES: GEO
Similar Datasets
Project description:The accessibility chromatin patterns during hPGCLCs undergo a diverse changes in absence of SOX15. The consequence of these changes lead to a somatic gene network activation that leads to decrease hPGCLC at late stage
2021-04-07 | GSE143344 | GEO
Project description:The accessibility chromatin patterns during hPGCLCs undergo a diverse changes in absence of SOX15. The consequence of these changes lead to a somatic gene network activation that leads to decrease hPGCLC at late stage
2021-04-07 | GSE143343 | GEO
Project description:Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study in vivo as it occurs immediately after blastocyst implantation. The establishment of in vitro human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase KDM2B in male fetal germ cells (FGCs) but not in male somatic cells. Besides, KDM2B shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of KDM2B in germ cell development. Although deletion of KDM2B had no significant effects on human embryonic stem cell (hESC)’s pluripotency, loss of KDM2B dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to KDM2B’s loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, KDM2B suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.
2021-01-10 | GSE160287 | GEO
Project description:Current human primordial germ cell like cells (hPGCLCs) differentiation methods from pluripotent stem cells (PSCs) are inefficient, and it is challenging to generate sufficient hPGCLCs to optimize the next steps to achieve in vitro gametogenesis. We present a new differentiation method that uses diluted basement membrane extract (BME) and low BMP4 concentration to induce efficient hPGCLC differentiation, in scalable 2D cell culture. We show that BME overlay potentiates BMP/SMAD signaling, induced lumenogenesis and increases expression of key hPGCLC progenitor markers such as TFAP2A, EOMES, GATA3 and CDX2. These findings highlight the importance of factors in the BME in hPGCLC differentiation, and demonstrate the potential of the BME-overlay method as a new model for interrogating the formation of PGCs and amnion in humans.
2023-07-01 | GSE214521 | GEO
Project description:Mechanisms underlying human germ cell development are unclear, partly due to difficulties in studying human embryos and lack of suitable experimental systems. Here, we show that human induced pluripotent stem cells (hiPSCs) differentiate into incipient mesoderm-like cells (iMeLCs), which robustly generate human primordial germ cell-like cells (hPGCLCs) that can be purified using the surface markers EpCAM and INTEGRINα6. The transcriptomes of hPGCLCs and primordial germ cells (PGCs) isolated from non-human primates are similar, and although specification of hPGCLCs and mouse PGCs rely on similar signaling pathways, hPGCLC specification transcriptionally activates germline fate without transiently inducing eminent somatic programs. This includes genes important for naive pluripotency and repression of key epigenetic modifiers, concomitant with epigenetic reprogramming. Accordingly, BLIMP1, which represses somatic programs in mice, activates and stabilizes a germline transcriptional circuit and represses a default neuronal differentiation program. Together, these findings provide a foundation for understanding and reconstituting human germ cell development in vitro.
2015-07-20 | GSE67259 | GEO
Project description:Although molecular studies on the human reproduction are arising, mechanisms underlying human primordial germ cell (PGC) development have remained largely unknown. Here, we conducted custom CRISPR screening to identify a subset of key genes for acquisition and maintenance of PGC fate in humans, combined with in vitro system of hPGC-like cells (hPGCLCs). Among crucial candidates by screen analysis, we characterize AKT coactivator, TCL1A, as a progressive role in hPGCLC development. A mutant TCL1A downregulated gene expression related to translational control, followed by reduced global protein synthesis and proliferation consequently via depressing AKT-mTOR signaling pathway. Our study provides novel regulators critical to hPGCLC development and demonstrate the importance of translational control in human reproduction.
2023-05-12 | GSE202996 | GEO
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
2014-12-26 | E-GEOD-60138 | biostudies-arrayexpress
Project description:In vitro gametogenesis is the process of making germline cells from human pluripotent stem cells. The foundation of this model is the quality of the first progenitors called primordial germ cells (PGCs), which in vivo are specified during the peri-implantation window of human development. Here, we show using human embryo attachment culture that hPGC specification begins at day 12 post fertilization. Using single cell RNA-sequencing of hPGC-like cells (hPGCLCs) differentiated from pluripotent stem cells we discovered that hPGCLC specification involves resetting pluripotency towards a transitional state with shared characteristics between naïve and primed pluripotency followed by differentiation into lineage primed TFAP2A+ progenitors. Applying the germline trajectory to TFAP2C mutants reveals that TFAP2C functions in the TFAP2A+ progenitors upstream of PRDM1 to regulate the expression of SOX17. This serves to protect hPGCLCs from crossing the Weismann’s barrier to adopt somatic cell fates and therefore is an essential mechanism for successfully initiating in vitro gametogenesis.
2019-12-29 | GSE140021 | GEO
Project description:During development, human primordial germ cells (hPGCs) transition through a transcriptional and epigenetic state similar to pre-implantation epiblast cells called naive ground-state pluripotency. Diagnostic transcription factors that define this state include TFAP2C, KLF4, and TFCP2L1, with TFAP2C necessary for both establishment of the naive-like state in hPGC-like cells (hPGCLCs) as well as establishment and self-renewal of naive human embryonic stem cells (hESCs). Here, we show that KLF4 and TFCP2L1 are not required for hPGC specification or establishment of the naive-like state in hPGCLCs. Instead, KLF4 and TFCP2L1 are each required for reversion of primed hESCs to the self-renewing naive ground state. Additionally, TFCP2L1 but not KLF4 function after hPGC specification in the proliferation of the hPGCLC population.
2022-04-30 | GSE148717 | GEO
Project description:Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell‐like cells (hPGCLCs) derived from human‐induced pluripotent stem cells (hiPSCs) can be propagated to at least ~10^6‐fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC‐like transcriptome and preserve their genome‐wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50‐fold) and persist only around 1 week, yet undergo cell‐autonomous genome‐wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic‐reconstituted ovaries, expanded hPGCLCs initiate genome‐wide DNA demethylation and differentiate into oogonia/gonocyte‐like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.
2020-09-23 | GSE148415 | GEO