Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Genes Dev. 2018 Mar 1;32(5-6):324-326. doi: 10.1101/gad.314013.118.
Hematopoietic stem cells (HSCs) reside and are maintained in specialized microenvironments within the bone marrow known as niches, which are comprised of various cell types. Among them, leptin receptor (LepR)-expressing CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells are known to create a niche for HSCs and at the same time to give rise to osteoblasts. These two functions of CAR/LepR cells appear to be tightly but inversely regulated to ensure adequate physical space for HSCs. However, how osteogenesis is prevented in CAR cells to maintain spaces available for HSCs and hematopoiesis remains unclear. In this issue of , Seike and colleagues (pp. 359-372) report that the transcription factor early B-cell factor () is preferentially expressed by CAR/LepR cells and inhibits CAR cell differentiation into osteoblasts while at the same time maintaining self-renewal of CAR/LepR cells. Using conditional knockout and retroviral systems, the investigators show that loss of in CAR cells impairs HSC numbers and leads to osteosclerosis. This study provides novel insights into transcriptional requirements for CAR cell bone formation by identifying Ebf3 as a niche factor secreted from CAR/Lepr cells that regulates the interplay between osteogenesis and hematopoiesis.
造血干细胞 (HSCs) 存在于骨髓中的特定微环境中，称为龛，由各种细胞类型组成。其中，瘦素受体 (LepR) 表达的 CXC 趋化因子配体 12 (CXCL12)-丰富的网状 (CAR) 细胞已知为 HSCs 创造龛，并同时产生成骨细胞。CAR/LepR 细胞的这两个功能似乎是紧密但相反地调节的，以确保 HSCs 有足够的物理空间。然而，CAR 细胞如何防止成骨以维持可用的 HSCs 和造血空间仍然不清楚。在本期杂志上，Seike 及其同事（第 359-372 页）报告说，早期 B 细胞因子 (Ebf3) 转录因子优先由 CAR/LepR 细胞表达，可抑制 CAR 细胞向成骨细胞分化，同时维持 CAR/LepR 细胞的自我更新。研究人员使用条件性敲除和逆转录病毒系统表明，CAR 细胞中缺失会损害 HSC 数量并导致骨质硬化。这项研究通过鉴定 Ebf3 作为一种由 CAR/Lepr 细胞分泌的龛因子，为 CAR 细胞骨形成的转录要求提供了新的见解，该因子调节成骨作用和造血作用之间的相互作用。
