Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow.

Stefano Comazzetto, Malea M. Murphy, Stefano Bertone, Elise Jeffery, Zhiyu Zhao, Sean J. Morrison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)477-486
Number of pages10
JournalCell Stem Cell
Volume24
Issue number3
Early online date17 Jan 2019
DOIs
Publication statusPublished - 7 Mar 2019

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