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Single cell analysis of emergent haematopoiesis in the human fetal bone marrow (10X)

ABSTRACT: 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.

INSTRUMENT(S): Illumina NovaSeq 6000, Chromium 10X Controller

ORGANISM(S): Homo sapiens

SUBMITTER: Muzlifah Haniffa

PROVIDER: E-MTAB-10042 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Single cell analysis of emergent haematopoiesis in the human fetal bone marrow (10X)

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

Single cell analysis of emergent haematopoiesis in the human fetal bone marrow (SS2)

2021-07-15 | E-MTAB-9801 | biostudies-arrayexpress

Blood and immune cell development in human fetal bone marrow and in Down syndrome

Project description:Throughout postnatal life, haematopoiesis in the bone marrow (BM) maintains blood and immune cell production. Haematopoiesis first emerges in human BM at 11-12 post conception weeks while fetal liver (FL) haematopoiesis is still expanding. Yet, almost nothing is known about how fetal BM evolves to meet the highly specialised needs of the fetus and newborn infant. Here, we detail the development of fetal BM including stroma using single cell RNA-sequencing. We find that the full blood and immune cell repertoire is established in fetal BM in a short time window of 6-7 weeks early in the second trimester. Fetal BM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. B-lymphocytes expansion occurs, in contrast with erythroid predominance in FL at the same gestational age. We identify transcriptional and functional differences that underlie tissue-specific identity and cellular diversification in fetal BM and FL. Finally, we reveal selective disruption of B-lymphocyte, erythroid and myeloid development due to cell intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in the fetal BM from constitutional chromosome anomaly Down syndrome during this crucial developmental time window.

2021-07-09 | GSE166895 | GEO

HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA

Project description:The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.

2023-08-01 | GSE210868 | GEO

Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium

Project description:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We use human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human yolk-sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of yolk sac-like primitive erythropoiesis, but no yolk sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a yolk sac-like SOX17- haemogenic endothelial intermediate.

2020-11-11 | GSE124085 | GEO

Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium

2020-11-11 | GSE124084 | GEO

The role of the yolk sac in human fetal development and identification of a hepatocyte-like cell in the human yolk sac (SS2)

Project description:The human yolk sac (YS) is an extra-embryonic tissue critical for early prenatal life development. It is the first site of haematopoiesis where progenitors differentiate from endoderm within blood islands of the yolk sac contributing initially to primitive erythropoiesis and in subsequent waves to erythro-myeloid and lymphoid differentiation.

2023-03-01 | E-MTAB-10888 | biostudies-arrayexpress

The role of the yolk sac in human fetal development and identification of a hepatocyte-like cell in the human yolk sac

2023-03-01 | E-MTAB-10552 | biostudies-arrayexpress

Effect of Ythdf2 in haematopoiesis

Project description:Effect of Ythdf2 in haematopoiesis

| PRJNA595576 | ENA

GATA2 mitotic bookmarking is required for definitive haematopoiesis [ChIP-seq]

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

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