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A trio of bipotent precursors seeds the mesenchymal, haematopoietic, and endothelial lineages of the yolk sac

ABSTRACT: During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro has revealed a mesenchymal differentiation potential, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct bipotential precursors: the haemangioblast, mesenchymoangioblast, and a novel cell type: the haematomesoblast. Between E6.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories.

ORGANISM(S): Mus musculus

PROVIDER: GSE204896 | GEO | 2022/12/21

REPOSITORIES: GEO

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In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis

Project description:During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro revealed the capacity for mesenchymal differentiation, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct precursors with dual-lineage outcomes: the haemangioblast, the mesenchymoangioblast, and a previously undescribed cell type: the haematomesoblast. Between E5.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories.

2022-12-21 | GSE164336 | 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.

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

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Erythro-myeloid progenitors contribute endothelial cells to developing blood vessels

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LMO2 Is Required for TAL1 DNA Binding Activity and Initiation of Definitive Haematopoiesis at the Haemangioblast Stage

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Project description:During embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages, however, the precise roles of Etv2 in yolk sac development remains unclear. We carried out a transcriptome analysis using an ES cell line that can inducibly express Etv2. Cells were induced for 12 hours at day 3 of differentiation.

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Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium

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