Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Cells. 2024 May 24;13(11):910. doi: 10.3390/cells13110910.
The bone marrow (BM) stromal cell microenvironment contains non-hematopoietic stromal cells called mesenchymal stromal cells (MSCs). MSCs are plastic adherent, form CFU-Fs, and give rise to osteogenic, adipogenic, chondrogenic progenitors, and most importantly provide HSC niche factor chemokine C-X-C motif ligand 12 (CXCL12) and stem cell factor (SCF). Different authors have defined different markers for mouse MSC identification like PDGFRSca-1 subsets, Nestin, or LepR cells. Of these, the LepR cells are the major source of SCF and CXCL12 in the BM microenvironment and play a major role in HSC maintenance and hematopoiesis. LepR cells give rise to most of the bones and BM adipocytes, further regulating the microenvironment. In adult BM, LepR cells are quiescent but after fracture or irradiation, they proliferate and differentiate into mesenchymal lineage osteogenic, adipogenic and/or chondrogenic cells. They also play a crucial role in the steady-state hematopoiesis process, as well as hematopoietic regeneration and the homing of hematopoietic stem cells (HSCs) after myeloablative injury and/or HSC transplantation. They line the sinusoidal cavities, maintain the trabeculae formation, and provide the space for HSC homing and retention. However, the LepR cell subset is heterogeneous; some subsets have higher adipogenic potential, while others express osteollineage-biased genes. Different transcription factors like Early B cell factor 3 (EBF3) or RunX2 help maintain this balance between the self-renewing and committed states, whether osteogenic or adipogenic. The study of LepR MSCs holds immense promise for advancing our understanding of HSC biology, tissue regeneration, metabolic disorders, and immune responses. In this review, we will discuss the origin of the BM resident LepR cells, different subtypes, and the role of LepR cells in maintaining hematopoiesis, osteogenesis, and BM adipogenesis following their multifaceted impact.
骨髓（BM）基质细胞微环境包含非造血基质细胞，称为间充质基质细胞（MSCs）。MSCs 是塑性贴壁细胞，形成 CFU-Fs，并产生成骨、成脂、成软骨祖细胞，最重要的是提供造血干细胞龛因子趋化因子 C-X-C 基序配体 12（CXCL12）和干细胞因子（SCF）。不同的作者已经定义了用于鉴定小鼠 MSC 的不同标记物，如 PDGFRSca-1 亚群、Nestin 或 LepR 细胞。其中，LepR 细胞是 BM 微环境中 SCF 和 CXCL12 的主要来源，在 HSC 维持和造血中发挥重要作用。LepR 细胞产生大多数骨骼和 BM 脂肪细胞，进一步调节微环境。在成年 BM 中，LepR 细胞处于静止状态，但在骨折或辐射后，它们增殖并分化为间充质谱系成骨、成脂和/或软骨细胞。它们在稳态造血过程中以及造血干细胞（HSCs）在骨髓清除性损伤和/或 HSC 移植后的再生和归巢中也起着至关重要的作用。它们排列在窦状腔中，维持小梁形成，并为 HSC 归巢和保留提供空间。然而，LepR 细胞亚群是异质的；一些亚群具有更高的成脂潜力，而其他亚群表达成骨谱系偏向基因。不同的转录因子，如早期 B 细胞因子 3（EBF3）或 RunX2，有助于维持这种自我更新和定向状态之间的平衡，无论是成骨还是成脂。LepR MSC 的研究为深入了解 HSC 生物学、组织再生、代谢紊乱和免疫反应提供了巨大的希望。在这篇综述中，我们将讨论 BM 驻留 LepR 细胞的起源、不同亚型以及 LepR 细胞在维持造血、成骨和 BM 脂肪生成方面的作用，以及它们在多方面的影响。
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