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Unraveling the role of human TSC-specific TFs [RNA-Seq]

ABSTRACT: Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208538 | GEO | 2023/03/22

REPOSITORIES: GEO

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Unraveling the role of human TSC-specific TFs [ChIP-Seq]

Project description:Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.

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Super-enhancer-guided decoding of gene regulatory networks in trophoblast stem cells

Project description:Cells belonging to trophoblast lineage are required for proper implantation and placentation, as well as the vascular, hematopoietic, and immunological properties of the placenta, a crucial organ mediating dynamic interactions between maternal and fetal tissues. Defects in trophoblast lineage development can cause early pregnancy failure or other pregnancy-related disorders. Despite its pivotal roles, the placenta remains as one of the least studied organs. Until now, only a handful of trophoblast-specific transcription factors (TFs) have been characterized, and underlying regulatory mechanisms modulating trophoblast lineage development remain poorly understood. Here we explore trophoblast stem cell (TSC)-specific super-enhancers (SEs) and subsequently identify SE-associated factors enriched with previously known and many unknown TFs modulating trophoblast lineage development. By mapping direct targets of 28 TSC-specific TFs in TSCs, we construct highly intertwined transcriptional regulatory networks where TFs are co-regulated and linked with signaling pathways, and which function as cellular modules dedicated to trophoblast lineage development. Additionally, we reveal that TSC-specific TFs alter their target sites corresponding to the reshaped enhancers during TSC differentiation. These findings advance our understanding on placenta biology.

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Unraveling the role of human TSC-specific TFs

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

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Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (ChIP-seq)

Project description:The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggest that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immuninty TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3 and MSX2 on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, the usb-family composition of MER41-derived enhancers that are active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of trophoblast TFs. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived placental enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by enhancers derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression in human TSCs. Overall, this study characterized the prevalent binding of GATA2/3, MSX2 and their co-factors on ERV-derived enhancers in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.

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Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (RNA-seq)

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