Landscape of TFs binding in mouse early embryos [Bisulfite-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE248696 | GEO | 2024/03/03
REPOSITORIES: GEO
Similar Datasets
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE228361 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212567 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212565 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212566 | GEO
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
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 | GSE154688 | GEO
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.
2021-02-15 | GSE154691 | GEO
Project description:The germ cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have established a culture system that recapitulates the mouse germ-cell specification pathway: Using cytokines, embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) are induced into epiblast-like cells (EpiLCs) and then into primordial germ cell-like cells (PGCLCs) with capacity both for spermatogenesis and oogenesis, creating an opportunity for understanding and regulating mammalian germ cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous over-expression of three transcription factors (TFs), Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2γ), directs EpiLCs, but not ESCs, swiftly and highly efficiently into a PGC state with endogenous transcription circuitry. The induction of the PGC state on EpiLCs minimally requires Prdm14 but not Blimp1 or Tfap2c. The TF-induced PGC state reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC specification in vivo and in vitro by cytokines including BMP4. Importantly, the TF-induced PGC-like cells robustly contribute to spermatogenesis and fertile offspring. Our findings provide not only a novel insight into the transcriptional logic that creates a germ cell state, but also a foundation for the TF-based reconstitution and regulation of mammalian gametogenesis. Aim of this analysis is characterization of transcription factor-induced primordial germ cells (TF-PGCLCs) compared with cytokine-induced primordial germ cells (Ck-PGCLCs) (Hayashi et al., 2011, Cell), epiblast-like cells (EpiLCs) (Hayashi et al., 2011, Cell), and embryonic stem cells (ESCs) and identification of genes differentially expressed among them. TF-PGCLCs induced by multiple combinations of TFs (Blimp1 (B), Prdm14 (P14), and Tfap2c (A) (BP14A), BP14, P14A, P14) on day 2 and 4 (for BP14A cells) of the induction were also compared. Parental clone without exogenous TFs cultured with doxycycline, are also included as a negative control. Ck-PGCLCs day 2 and day 4 samples, which are previously unreported, EpiLCs and ESCs used in this study were also included. Overexpression of exogenous three TFs in ESCs yields stella-ECFP (SC) positive cells, which were sorted and included in the analysis. cDNA samples, prepared from approximately 20,000 cells, were amplified with a quantitative global PCR method (Kurimoto et al., 2006, Nucleic Acids Research). Two biological duplicates for each cell type were analyzed. Samples from GSE30056 were also included and reanalysed (GSM1070855-GSM1070864).
2013-08-04 | E-GEOD-43775 | biostudies-arrayexpress
Project description:During the first lineage segregation, a mammalian totipotent embryo differentiates into inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first mouse lineage specification across 6 stages, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found TFAP2C, a trophoblast regulator, bound and activated both early TE and ICM genes at the totipotent (2-8-cell) stages (“bipotency activation”). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, Tdgf1, and early TE genes, including Tfeb and Itgb5 in 8-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early-ICM genes but acquired binding to late-TE genes in blastocysts where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, “bipotency activation” in totipotent embryos also applied to a pluripotency regulator NR5A2 which similarly bound and activated both ICM and TE lineage genes at the 8-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.
2023-11-23 | GSE216256 | GEO
Project description:In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-likefamilymember1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.
2024-01-05 | GSE252377 | GEO