@article{fa4fb56ded044cbf9c8fd53d3944b4c6,
title = "Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow",
abstract = " Hematopoietic stem cells (HSCs) are maintained in a perivascular niche in bone marrow, in which leptin receptor + (LepR) stromal cells and endothelial cells synthesize factors required for HSC maintenance, including stem cell factor (SCF). An important question is why LepR + cells are one hundred times more frequent than HSCs. Here, we show that SCF from LepR + cells is also necessary to maintain many c-kit + -restricted hematopoietic progenitors. Conditional deletion of Scf from LepR + cells depleted common myeloid progenitors (CMPs), common lymphoid progenitors (CLPs), granulocyte-macrophage progenitors (GMPs), megakaryocyte-erythrocyte progenitors (MEPs), pre-megakaryocyte-erythrocyte progenitors (PreMegEs), and colony-forming units-erythroid (CFU-Es), as well as myeloid and erythroid blood cells. This was not caused by HSC depletion, as many other restricted progenitors were unaffected. Moreover, Scf deletion from endothelial cells depleted HSCs, but not progenitors. Early erythroid progenitors were closely associated with perisinusoidal LepR + cells. This reveals cellular specialization within the niche: SCF from LepR + cells is broadly required by HSCs and restricted progenitors while SCF from endothelial cells is required mainly by HSCs. Bone marrow hematopoietic stem cells reside in perivascular niches associated with sinusoids and require factors from leptin receptor + stromal cells and endothelial cells. Morrison and colleagues show that c-kit + -restricted hematopoietic progenitors also require Stem Cell Factor made by LepR + cells, but not endothelial cells. At least some of these restricted progenitors reside in perisinusoidal niches.",
keywords = "endothelial cells, erythropoiesis, leptin receptor stromal cells, niche, restricted hematopoietic progenitors, sinusoid, stem cell factor",
author = "Stefano Comazzetto and Murphy, {Malea M.} and Stefano Berto and Elise Jeffery and Zhiyu Zhao and Morrison, {Sean J.}",
note = "Funding Information: S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the Kathryn and Gene Bishop Distinguished Chair in Pediatric Research, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. S.C. was supported by an EMBO Long-Term Fellowship (ALTF 722-2015). E.J. was a postdoctoral fellow of the Damon Runyon Cancer Research Foundation (DRG-2278-16). M.M.M. was supported by a National Research Service Award from the NIH (F32 HL124947). This work was funded by the National Institute on Aging (R37 AG024945), the National Heart, Lung, and Blood Institute (HL097760), and the Cancer Prevention and Research Institute of Texas. We thank Kati Ahlqvist for help with transplantation experiments as well as Jian Xu and Andrew DeVilbiss for helpful discussions. We thank N. Loof and the Moody Foundation Flow Cytometry Facility and A. Gross for mouse colony management. Funding Information: S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the Kathryn and Gene Bishop Distinguished Chair in Pediatric Research, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. S.C. was supported by an EMBO Long-Term Fellowship ( ALTF 722-2015 ). E.J. was a postdoctoral fellow of the Damon Runyon Cancer Research Foundation ( DRG-2278-16 ). M.M.M. was supported by a National Research Service Award from the NIH ( F32 HL124947 ). This work was funded by the National Institute on Aging ( R37 AG024945 ), the National Heart, Lung, and Blood Institute ( HL097760 ), and the Cancer Prevention and Research Institute of Texas . We thank Kati Ahlqvist for help with transplantation experiments as well as Jian Xu and Andrew DeVilbiss for helpful discussions. We thank N. Loof and the Moody Foundation Flow Cytometry Facility and A. Gross for mouse colony management. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = mar,
day = "7",
doi = "10.1016/j.stem.2018.11.022",
language = "English (US)",
volume = "24",
pages = "477--486.e6",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "3",
}