Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow

Chunliang Xu, Xin Gao, Qiaozhi Wei, Fumio Nakahara, Samuel E. Zimmerman, Jessica Mar and Paul S. Frenette ()
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Chunliang Xu: Albert Einstein College of Medicine
Xin Gao: Albert Einstein College of Medicine
Qiaozhi Wei: Albert Einstein College of Medicine
Fumio Nakahara: Albert Einstein College of Medicine
Samuel E. Zimmerman: Albert Einstein College of Medicine
Jessica Mar: Albert Einstein College of Medicine
Paul S. Frenette: Albert Einstein College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Endothelial cells (ECs) contribute to haematopoietic stem cell (HSC) maintenance in bone marrow, but the differential contributions of EC subtypes remain unknown, owing to the lack of methods to separate with high purity arterial endothelial cells (AECs) from sinusoidal endothelial cells (SECs). Here we show that the combination of podoplanin (PDPN) and Sca-1 expression distinguishes AECs (CD45− Ter119− Sca-1bright PDPN−) from SECs (CD45− Ter119− Sca-1dim PDPN+). PDPN can be substituted for antibodies against the adhesion molecules ICAM1 or E-selectin. Unexpectedly, prospective isolation reveals that AECs secrete nearly all detectable EC-derived stem cell factors (SCF). Genetic deletion of Scf in AECs, but not SECs, significantly reduced functional HSCs. Lineage-tracing analyses suggest that AECs and SECs self-regenerate independently after severe genotoxic insults, indicating the persistence of, and recovery from, radio-resistant pre-specified EC precursors. AEC-derived SCF also promotes HSC recovery after myeloablation. These results thus uncover heterogeneity in the contribution of ECs in stem cell niches.

Date: 2018
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DOI: 10.1038/s41467-018-04726-3

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