Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence

Abstract

Development of the dorsal aorta is a key step in the establishment of the adult bloodforming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Earlier studies in the chick showed that paraxial mesoderm generates another subset of endothelial cells that incorporate into the dorsal aorta to replace HSPCs as they exit the aorta and enter circulation. Here we show that a similar process occurs in the zebrafish, where a population of endothelial precursors delaminates from the somitic dermomyotome to incorporate exclusively into the developing dorsal aorta. Whereas somite-derived endothelial cells (SDECs) lack hematopoietic potential, they act as local niche to support the emergence of HSPCs from neighboring hemogenic endothelium. Thus, at least three subsets of endothelial cells (ECs) contribute to the developing dorsal aorta: vascular ECs, hemogenic ECs, and SDECs. Taken together, our findings indicate that the distinct spatial origins of endothelial precursors dictate different cellular potentials within the developing dorsal aorta.

Analyses of Avascular Mutants Reveal Unique Transcriptomic Signature of Non-conventional Endothelial Cells

“…Our fate map shows that ECs in avascular mutants do not originate from the ventral margin of the gastrula, the conventional source for ECs (Melby et al, 1996;Vogeli et al, 2006), but from the tailbud of the embryos approximately at 14 hpf, although we cannot formally exclude the possibility that a small percentage of these cells might have a different developmental origin. Our finding is consistent with previous reports that the tailbud harbors progenitors capable of generating the entire non-epidermal posterior body including ECs (Martin and Kimelman, 2012;Row et al, 2016), and in agreement with a recent report that npas4l −/− does not contain either LPM-or somite-derived ECs (Sahai-Hernandez et al, 2020). Considering that highly plastic progenitors, the PWPCs which are proposed to retain angiogenic potential, exist in the tailbud (Row et al, 2016), we speculate that these cells may give rise to ECs in avascular mutants.…”

Recent Advances in Developmental Hematopoiesis: Diving Deeper With New Technologies

“…The lack of hemogenic potential of the dorsal aortic endothelium of most other vertebrate species might also be explained by the different origin of the endothelial cells populating the ventral and the dorsal part of the aorta. In zebrafish embryos, the dorsal endothelium does not originate from the splanchnopleura (lateral plate mesoderm) but from the paraxial mesoderm (103). In the avian embryo, the dorsal endothelium that derives from the splanchnopleura is progressively replaced by paraxial mesoderm-derived endothelial cells (as the ventral endothelium), which corresponds to the end of aortic hematopoiesis (104)(105)(106).…”

Transcriptional activity of Npas4l controls endothelial lineage specification and restriction in zebrafish

“…Although the expression of endothelial reporters in paraxial mesoderm-derived muscle tissue is generally rejected as potential off-target fluorescence, there is mounting evidence of paraxial mesoderm-derived endothelial cells (compare section 1.2.1). The discovery of bipotent cells in the zebrafish paraxial mesoderm that can give rise to specialized hematopoietic stem cells Sahai-Hernandez et al, 2020) as well as the differentiation of etsrp reporter positive endothelial progenitors into skeletal muscle observed in etsrp mutants add plausibility to the observed patterns. In addition to this indirect evidence, McGarvey et al (2020) recently published a preprint showing tissue specific enhancers through single cell ATACseq in the promoter region of npas4l.…”

“…The paraxial mesoderm has been suggested to be an additional source of endothelial cells in various species (Couly et al, 1995;Wilting et al, 2000;Wasteson et al, 2008;Stone and Stainier, 2019). In zebrafish, the interaction with the paraxial mesoderm is required for the differentiation of hematopoietic cell progenitors (Rohde et al, 2004), and the paraxial mesoderm itself contains bipotent progenitors that can give rise to hematopoietic stem and progenitor cells or muscle progenitors Sahai-Hernandez et al, 2020). Also the endoderm has been suggested but not yet shown to give rise to endothelial cells.…”

“…The paraxial mesoderm has been suggested to be an additional source of endothelial cells (Couly et al, 1995;Wasteson et al, 2008;Stone and Stainier, 2019;Pak et al, 2020). In zebrafish, the paraxial mesoderm has been reported to be a source of a bipotent cell population that can give rise to hematopoietic stem and progenitor cells or muscle progenitors Sahai-Hernandez et al, 2020). Also, ectopic etsrp overexpression has been reported to trigger endothelial marker expression and behavior in cells of the paraxial mesoderm (Veldman et al, 2013).…”