Single-cell atlas of major haematopoietic tissues sheds light on blood cell formation from embryonic endothelium

Abstract

The Yolk Sac (YS) and Aorta-Gonad-Mesonephros (AGM) are two major haematopoietic regions during embryonic development. Interestingly, AGM is the only one generating haematopoietic stem cells (HSCs). To identify the difference between AGM and YS, we compared them using singlecell RNA sequencing between 9.5 and 11.5 days of mouse embryonic development and identified cell populations using CONCLUS, a new computational tool. The AGM was the only one containing neurons and a specific mesenchymal population, while the YS major component was an epithelial population expressing liver marker genes. In addition, the YS contained a major endothelial population expressing Stab2, a hyaluronan receptor, also highly expressed by liver endothelium. We demonstrated that the YS haematopoietic potential was restricted to Stab2negative cells and that ectopic expression of Stab2 could reduce blood cell formation from endothelium. Our results indicate that the AGM is a tissue more favourable to HSCs development than the YS because of its microenvironment and the nature of its endothelial cells.

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

“…The expression matrix was then processed through the CONCLUS pipeline 52 : https://github.com/lancrinlab/CONCLUS. We then generated t-SNE plots highlighting the expression pattern of Cdh5 and Cd44 genes ( Supplementary Fig.…”

Therapeutic correction of hemophilia A by transplantation of hPSC-derived liver sinusoidal endothelial cell progenitors

“…The efficient development of LSEC progenitors from the 12B4A-induced CD235a/b + mesoderm raises the interesting possibility that this endothelial lineage is specified early in development and may represent a ''primitive'' lineage, potentially related to the vasculature found in the yolk sac that directly drains to the embryonic liver via the vitelline veins. The finding that yolk sac ECs express genes associated with the LSEC lineage including LYVE1, STAB2, CD32B(FCGR2B), MRC1, and CD36 (Gordon et al, 2008;Hou et al, 2022;Lee et al, 2016;Popescu et al, 2019;Shvartsman et al, 2019;Van Handel et al, 2012) supports this notion and suggests that these two vasculatures may share both biomolecule scavenging functions and a common developmental program.…”

Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos

“…Gene Ontology terms related to angiogenesis were enriched in the endothelial-biased subpopulation, and ribosome biogenesis was enriched in the hematopoietic-biased subpopulation of yolk sac PK44 cells ( Figure 5F ). By further comparing the hematopoietic-biased subpopulations from the yolk sac and that from the AGM region, we detected a set of DEGs similar to those extracted from the comparison of PK44 cells between two sites ( Figure 5B ), including Lyve1 and Stab2 , which were relatively highly expressed in the former ( Nonaka et al, 2007 ; Lee et al, 2016 ; Ganuza et al, 2018 ; Shvartsman et al, 2019 ) ( Figure 5G ). Considering the unambiguous repopulating capacity of the progenies of PK44 cells from both the yolk sac and AGM region ( Figures 4F–H and Supplementary Figure 3A ), these data together suggest the existence of spatially and molecularly distinct HECs with a multilineage hematopoietic potential.…”

“…Of the 87 cells that passed the strict quality control, we detected, on average, 5139 genes and 248,722 transcripts for each cell. Of note, the well-known yolk sac endothelial markers Lyve1 and Stab2 were highly expressed in the PK44 cells from the yolk sac compared with those from AGM region (Nonaka et al, 2007;Lee et al, 2016;Ganuza et al, 2018;Shvartsman et al, 2019) (Figure 5B). The genes enriched in the yolk sac PK44 population compared with E10.0 AGM PK44 cells (Hou et al, 2020) were related to angiogenesis and vasculature development (Figure 5C).…”