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, Paul S. Frenette

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2449
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Stem Cell Factor
bone marrow
stem cells
Endothelial cells
Bone
Endothelial Cells
Bone Marrow
recovery
deletion
tracing
Stem cells
cells
antibodies
maintenance
isolation
purity
adhesion
Hematopoietic Stem Cells
Stem Cell Niche
molecules

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow. / Xu, Chunliang; Gao, Xin; Wei, Qiaozhi; Nakahara, Fumio; Zimmerman, Samuel E.; Mar, Jessica; Frenette, Paul S.

In: Nature Communications, Vol. 9, No. 1, 2449, 01.12.2018.

Research output: Contribution to journalArticle

Xu, Chunliang ; Gao, Xin ; Wei, Qiaozhi ; Nakahara, Fumio ; Zimmerman, Samuel E. ; Mar, Jessica ; Frenette, Paul S. / Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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