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Title:
Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow | Nature Communications
Description:
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. Endothelial cells (EC) are known to contribute to haematopoietic stem cell (HSC) maintenance in the bone marrow (BM). Here the authors demonstrate that arterial ECs can be distinguished from sinusoidal ECs by podoplanin and Sca-1 expression, and that specifically arterial, but not sinusoidal ECs maintain HSCs by secreting SCF.
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Keywords {🔍}
cells, aecs, secs, fig, mice, pubmed, cell, scf, article, ecs, stem, pdpn, expression, google, scholar, cat, cas, hsc, facs, analysis, nature, data, sca, hscs, clone, bmxcreert, endothelial, bone, marrow, cre, central, haematopoietic, ebioscience, niche, ter, supplementary, injected, nestingfp, expressed, arterial, niches, representative, bar, antibodies, analyses, eporcre, maintenance, revealed, regeneration, anticd,
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nature portfolio privacy policy thermo fisher scientific rosa26-loxp-stop-loxp-tdtomato translational research program pacific blue-anti-mouse cd54 advertising regenerative medicine research ve-cadherin− isolectin gs-ib4− pe-rat anti-mouse cd62e anti-cd31/anti-ve-cadherin showing social media pe-cy7-anti-mouse pdpn research support gender-matched littermate controls 3 μg pe-anti-mouse pdpn reprints effective library size original library size fluorescently-labelled anti-ve-cadherin sinusoidal radio-resistant precursors haematopoietic stem-cell maintenance scf fl/− littermate controls lymphoid-primed multipotent progenitor donkey anti-goat igg retro-orbital plexus bleeding dna libraries promote post-injury regeneration author information authors pe-cy7-anti-cd117 pe-cy7-anti-ki67 fluorescence-activated cell sorting bmx-creert2-labelled cells colocalise alexa fluor 700-anti-cd16/32 pe-cy7-anti-cd31 fluorescently-labelled isolectin b4 cultured akt-activated ecs radio-resistant endothelial precursors alexa fluor 647-anti-cd31 ng2+ peri-arteriolar fraction pe-anti-mouse pdpn cxcl12-cxcr4 chemokine signaling alexa fluor 647-anti-cd144 haematopoietic stem cell hematopoietic stem cells 1 mg ml−1 collagenase iv aec-derived scf contributes nestin-gfp-labelled cells apc-efluor780-anti-cd45r c-kit+ cells
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headline:Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow
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description: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 (CD45â Ter119â Sca-1bright PDPNâ) from SECs (CD45â Ter119â 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. Endothelial cells (EC) are known to contribute to haematopoietic stem cell (HSC) maintenance in the bone marrow (BM). Here the authors demonstrate that arterial ECs can be distinguished from sinusoidal ECs by podoplanin and Sca-1 expression, and that specifically arterial, but not sinusoidal ECs maintain HSCs by secreting SCF.
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