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

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Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-01-17 , DOI: 10.1016/j.stem.2018.11.022
Stefano Comazzetto ₁ , Malea M Murphy ₁ , Stefano Berto ₂ , Elise Jeffery ₁ , Zhiyu Zhao ₁ , Sean J Morrison ₃

Affiliation

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.

中文翻译：

限制性造血祖细胞和红细胞生成需要来自骨髓中瘦素受体 + 利基细胞的 SCF。

造血干细胞 (HSC) 维持在骨髓的血管周围生态位中，其中瘦素受体 + (LepR) 基质细胞和内皮细胞合成 HSC 维持所需的因子，包括干细胞因子 (SCF)。一个重要的问题是为什么 LepR+ 细胞的频率是 HSC 的一百倍。在这里，我们表明来自 LepR+ 细胞的 SCF 也是维持许多 c-kit+ 限制性造血祖细胞所必需的。从 LepR+ 细胞中条件性删除 Scf 耗尽了常见的骨髓祖细胞 (CMP)、常见的淋巴祖细胞 (CLP)、粒细胞-巨噬细胞祖细胞 (GMP)、巨核细胞-红细胞祖细胞 (MEP)、前巨核细胞-红细胞祖细胞 (MEP)、前巨核细胞-红细胞祖细胞 (M -形成单位-红细胞（CFU-Es），以及髓系和红细胞系血细胞。这不是由 HSC 耗尽引起的，因为许多其他受限制的祖先不受影响。此外，内皮细胞的Scf缺失消耗了HSC，但不消耗祖细胞。早期红系祖细胞与窦周 LepR+ 细胞密切相关。这揭示了生态位内的细胞特化：HSC 和受限祖细胞广泛需要来自 LepR+ 细胞的 SCF，而 HSC 主要需要来自内皮细胞的 SCF。

更新日期：2019-01-17

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