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Abstract

The contribution of endocardial cells (EdCs) to the hematopoietic
lineages has been strongly debated. Here, we provide evidence that in
zebrafish, the endocardium gives rise to and maintains a stable
population of hematopoietic cells. Using single-cell sequencing, we
identify an endocardial subpopulation expressing enriched levels of
hematopoietic-promoting genes. High-resolution microscopy and
photoconversion tracing experiments uncover hematopoietic cells, mainly
hematopoietic stem and progenitor cells (HSPCs)/megakaryocyte-erythroid
precursors (MEPs), derived from EdCs as well as the dorsal aorta stably
attached to the endocardium. Emergence of HSPCs/MEPs in hearts cultured
ex vivo without external hematopoietic sources, as well as longitudinal
imaging of the beating heart using light sheet microscopy, support
endocardial contribution to hematopoiesis. Maintenance of these
hematopoietic cells depends on the adhesion factors Integrin alpha 4 and
Vcam1 but is at least partly independent of cardiac trabeculation or
shear stress. Finally, blocking primitive erythropoiesis increases
cardiac-residing hematopoietic cells, suggesting that the endocardium is
a hematopoietic reservoir. Altogether, these studies uncover the
endocardium as a resident tissue for HSPCs/MEPs and a de novo source of
hematopoietic cells.
The endocardium lines the interior of the heart chambers and has been
debated as a source of hematopoietic lineages. Here they show that the
endocardium may act as a source of, and resident tissue for,
hematopoietic stem and progenitor cells in zebrafish, providing evidence
for diversity in origins and residences of hematopoietic cells.