Hematopoietic stem cells derive directly from aortic endothelium during development

By Julien Y. Bertrand, N. Chi, B. Santoso, Shutian Teng, D. Stainier, D. Traver. Nature, 2010

1,020 citations recorded by the source corpus.

A major goal of regenerative medicine is to instruct formation of multipotent, tissue-specific stem cells from induced pluripotent stem cells (iPSCs) for cell replacement therapies. Generation of haematopoietic stem cells (HSCs) from iPSCs or embryonic stem cells (ESCs) is not currently possible, however, necessitating a better understanding of how HSCs normally arise during embryonic development. We previously showed that haematopoiesis occurs through four distinct waves during zebrafish development, with HSCs arising in the final wave in close association with the dorsal aorta. Recent reports have suggested that murine HSCs derive from haemogenic endothelial cells (ECs) lining the aortic floor. Additional in vitro studies have similarly indicated that the haematopoietic progeny of ESCs arise through intermediates with endothelial potential. Here we have used the unique strengths of the zebrafish embryo to image directly the generation of HSCs from the ventral wall of the dorsal aorta. Using combinations of fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry, we have identified and isolated the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. Finally, using a permanent lineage tracing strategy, we demonstrate that the HSCs generated from haemogenic endothelium are the lineal founders of the adult haematopoietic system.

Subfields: Cell Biology, Immunology

View Paper: https://www.semanticscholar.org/paper/1a32dc0ff1c6710d8c6c82d5e2e8dec97696726d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Leonard I. Zon
2. J. Pollard
3. Florent Ginhoux

In Immunology

1. Marco Prinz
2. J. Pollard
3. F. Geissmann
4. A. Mantovani
5. Lisa M. Coussens
6. J. Joyce
7. D. Hanahan
8. A. Sica

Citations in the corpus

• Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches (2022, neutral): “, 2010); Tg(actb2:loxP-STOP-loxP-DsRed) (Bertrand et al., 2010) enabling macs to be sorted for sequencing as DsRed, GFP double positive cells.”
• A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells (2012, background): “1 -/mice (4), B6 Flt3-Cre mice (5), B6 Mx1-Cre mice (6), FVB Tg(Csf1r Mer-iCre-Mer ) 1Jwp mice (7), and B6 Gt(ROSA)26Sor tm1(EYFP)Cos /J (Rosa26 LSL-YFP ) (8) have been previously described.”
• EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay (2017, methodology): “8% low–melting point agarose or 4% methylcellulose containing 160 mg/L tricaine as previously described (Bertrand et al., 2010).”