Fate tracing reveals the endothelial origin of hematopoietic stem cells

By A. Zovein, Jennifer J. Hofmann, M. Lynch, W. J. French, K. Turlo, Yanan Yang, Michael S. Becker, L. Zanetta, E. Dejana, J. Gasson and 2 more. Cell Stem Cell, 2008

690 citations recorded by the source corpus.

Summary Hematopoietic stem cells (HSCs) originate within the aorta-gonado-mesonephros (AGM) region of the midgestation embryo, but the cell type responsible for their emergence is unknown since critical hematopoietic factors are expressed in both the AGM endothelium and its underlying mesenchyme. Here we employ a temporally restricted genetic tracing strategy to selectively label the endothelium, and separately its underlying mesenchyme, during AGM development. Lineage tracing endothelium, via an inducible VE-cadherin Cre line, reveals that the endothelium is capable of HSC emergence. The endothelial progeny migrate to the fetal liver, and later to the bone marrow, are capable of expansion, self-renewal, and multi-lineage hematopoietic differentiation. HSC capacity is exclusively endothelial, as ex vivo analyses demonstrate lack of VE-cadherin Cre induction in circulating and fetal liver hematopoietic populations. Moreover, AGM mesenchyme, as selectively traced via a myocardin Cre line, is incapable of hematopoiesis. Our genetic tracing strategy therefore reveals an endothelial origin of HSCs.

Subfields: Cell Biology, Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3ca3480fe5be7cbafce932840628388a225a3765

Citations in the corpus

• Hematopoietic stem cells derive directly from aortic endothelium during development (2010, neutral): “Furthermore, experiments utilizing an inducible Cdh5:Cre ERT2 transgene suggested that ECs within the region flanked by the aorta, gonads and mesonephros (AGM) in the midgestation mouse embryo contained the majority of HSC potential 1 .”