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

Author

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  • Chunliang Xu

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Xin Gao

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Qiaozhi Wei

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Fumio Nakahara

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Samuel E. Zimmerman

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Jessica Mar

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Paul S. Frenette

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

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.

Suggested Citation

  • Chunliang Xu & Xin Gao & Qiaozhi Wei & Fumio Nakahara & Samuel E. Zimmerman & Jessica Mar & Paul S. Frenette, 2018. "Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04726-3
    DOI: 10.1038/s41467-018-04726-3
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    Cited by:

    1. Joschka Heil & Victor Olsavszky & Katrin Busch & Kay Klapproth & Carolina Torre & Carsten Sticht & Kajetan Sandorski & Johannes Hoffmann & Hiltrud Schönhaber & Johanna Zierow & Manuel Winkler & Christ, 2021. "Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Runfeng Miao & Harim Chun & Xing Feng & Ana Cordeiro Gomes & Jungmin Choi & João P. Pereira, 2022. "Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Taghreed Hirz & Shenglin Mei & Hirak Sarkar & Youmna Kfoury & Shulin Wu & Bronte M. Verhoeven & Alexander O. Subtelny & Dimitar V. Zlatev & Matthew W. Wszolek & Keyan Salari & Evan Murray & Fei Chen &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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