TY - JOUR
T1 - Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow
AU - Xu, Chunliang
AU - Gao, Xin
AU - Wei, Qiaozhi
AU - Nakahara, Fumio
AU - Zimmerman, Samuel E.
AU - Mar, Jessica
AU - Frenette, Paul S.
N1 - Funding Information:
This work was supported by R01 grants from the National Institutes of Health (NIH) (DK056638, HL069438, DK116312, DK112976 to P. S.F.). We are also grateful to the New York State Department of Health (NYSTEM Program) for shared facility (C029154) and research support (N13G-262) and the Leukemia and Lymphoma Society's Translational Research Program
Funding Information:
We thank C. Prophete and P. Ciero for technical assistance and L. Tesfa, Y. Wang, and D. Sun for help with cell sorting. We thank Drs. R. Adams, T. Nagasawa, and S. Morrison for providing genetically modified mice. This work was supported by R01 grants from the National Institutes of Health (NIH) (DK056638, HL069438, DK116312, DK112976 to P. S.F.). We are also grateful to the New York State Department of Health (NYSTEM Program) for shared facility (C029154) and research support (N13G-262) and the Leukemia and Lymphoma Society’s Translational Research Program.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-04726-3
DO - 10.1038/s41467-018-04726-3
M3 - Article
C2 - 29934585
AN - SCOPUS:85048945892
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2449
ER -