EZH1 as a key epigenetic barrier to definitive haematopoiesis during embryonic development
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PROVIDER: PRJNA352132 | ENA |
REPOSITORIES: ENA
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Project description:Blood develops in distinct stages. Haematopoietic progenitors in the embryo manifest restricted differentiation potential relative to definitive haematopoietic stem cells in adult bone marrow, which support lifelong multilineage haematopoiesis. To identify regulators of embryonic haematopoiesis, we screened chromatin modifiers and identified the Polycomb group protein EZH1 as a barrier to multilineage potential from pluripotent stem cells (PSCs). EZH1 was directly bound to bivalently poised, yet restricted, HSC and lymphoid genes in primitive progenitors; knockdown enabled robust generation of multilineage progenitors. Moreover, EZH1 haploinsufficiency promoted the generation of HSCs with long-term, multilineage and self-renewal potential from sites of embryonic haematopoiesis in vivo. Together, this work identifies EZH1 as a key epigenetic barrier to definitive haematopoiesis during embryonic development, and highlights the utility of chromatin modifiers as cell engineering targets to enhance blood differentiation from PSCs.
2018-01-01 | GSE89415 | GEO
Project description:Blood develops in distinct stages. Haematopoietic progenitors in the embryo manifest restricted differentiation potential relative to definitive haematopoietic stem cells in adult bone marrow, which support lifelong multilineage haematopoiesis. To identify regulators of embryonic haematopoiesis, we screened chromatin modifiers and identified the Polycomb group protein EZH1 as a barrier to multilineage potential from pluripotent stem cells (PSCs). EZH1 was directly bound to bivalently poised, yet restricted, HSC and lymphoid genes in primitive progenitors; knockdown enabled robust generation of multilineage progenitors. Moreover, EZH1 haploinsufficiency promoted the generation of HSCs with long-term, multilineage and self-renewal potential from sites of embryonic haematopoiesis in vivo. Together, this work identifies EZH1 as a key epigenetic barrier to definitive haematopoiesis during embryonic development, and highlights the utility of chromatin modifiers as cell engineering targets to enhance blood differentiation from PSCs.
2018-01-01 | GSE89417 | GEO
Project description:Blood develops in distinct stages. Haematopoietic progenitors in the embryo manifest restricted differentiation potential relative to definitive haematopoietic stem cells in adult bone marrow, which support lifelong multilineage haematopoiesis. To identify regulators of embryonic haematopoiesis, we screened chromatin modifiers and identified the Polycomb group protein EZH1 as a barrier to multilineage potential from pluripotent stem cells (PSCs). EZH1 was directly bound to bivalently poised, yet restricted, HSC and lymphoid genes in primitive progenitors; knockdown enabled robust generation of multilineage progenitors. Moreover, EZH1 haploinsufficiency promoted the generation of HSCs with long-term, multilineage and self-renewal potential from sites of embryonic haematopoiesis in vivo. Together, this work identifies EZH1 as a key epigenetic barrier to definitive haematopoiesis during embryonic development, and highlights the utility of chromatin modifiers as cell engineering targets to enhance blood differentiation from PSCs.
2018-01-01 | GSE89416 | GEO
Project description:In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.
2023-06-27 | GSE207551 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-01 | GSE89418 | GEO
Project description:Haematopoeisis emerges in the human fetal bone marrow (BM) at around 12 post conception weeks. This constitutes the second wave of definitive haematopoiesis following on from the first wave in fetal liver from around 6 post conception weeks. The BM emerges as the dominant site of haematopoiesis, responsible for lifelong blood and immune cell production. Yet, little is known about how the composition of the fetal BM, the microenvironment permissive to establishing haematopoiesis and the interplay with other sites of fetal haematopoiesis in fetal health or disease. Herein we utilise single cell RNA sequencing to describe fetal haematopoeisis throughout gestation and better understand the development of the human immune system.
2021-07-06 | E-MTAB-9389 | biostudies-arrayexpress
Project description:Haematopoeisis emerges in the human fetal bone marrow (BM) at around 12 post conception weeks. This constitutes the second wave of definitive haematopoiesis following on from the first wave in fetal liver from around 6 post conception weeks. The BM emerges as the dominant site of haematopoiesis, responsible for lifelong blood and immune cell production. Yet, little is known about how the composition of the fetal BM, the microenvironment permissive to establishing haematopoiesis and the interplay with other sites of fetal haematopoiesis in fetal health or disease. Herein we utilise single cell RNA sequencing to describe fetal haematopoeisis throughout gestation and better understand the development of the human immune system.
2021-07-15 | E-MTAB-9801 | biostudies-arrayexpress
Project description:Haematopoeisis emerges in the human fetal bone marrow (BM) at around 12 post conception weeks. This constitutes the second wave of definitive haematopoiesis following on from the first wave in fetal liver from around 6 post conception weeks. The BM emerges as the dominant site of haematopoiesis, responsible for lifelong blood and immune cell production. Yet, little is known about how the composition of the fetal BM, the microenvironment permissive to establishing haematopoiesis and the interplay with other sites of fetal haematopoiesis in fetal health or disease. Herein we utilise single cell RNA sequencing and surface protein characterisation using CITE-seq technology to describe fetal haematopoeisis throughout gestation and better understand the development of the human immune system.
2021-07-15 | E-MTAB-10042 | biostudies-arrayexpress
Project description:In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.
2023-06-27 | GSE221691 | GEO
Project description:Polycomb group (PcG) proteins initiate the formation of repressed chromatin domains and regulate developmental gene expression. A mammalian PcG protein, Enhancer of Zeste homolog 2 (Ezh2), triggers transcriptional repression by catalyzing the addition of methyl groups onto lysine-27 of histone H3 (H3K27me2/3)1. This action facilitates the binding of other PcG proteins to histone H3 and compaction of chromatin. Interestingly, there exists a paralog of Ezh2, termed Ezh1, whose primary function remains unclear. Here, we provide evidence for genome-wide association of Ezh1 with active epigenetic marks, RNA polymerase II (PolII) and mRNA production. Ezh1 depletion reduced global PolII occupancy within gene bodies and resulted in delayed transcriptional activation during differentiation of skeletal muscle cells. Conversely, ectopic expression of wild-type Ezh1 led to premature gene activation and rescued PolII-elongation defects in Ezh1-depleted cells. Collectively, these findings reveal an unanticipated role of a PcG protein in promoting mRNA transcription. Examination of 3 different histone modifications, 3 modified forms of RNA polymerase II, Ezh1, Ezh2 and mRNA levels in a skeletal muscle cells at various developmental stages.
2011-11-23 | E-GEOD-25549 | biostudies-arrayexpress