McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Cell Stem Cell. 2013 Aug 1;13(2):175-89. doi: 10.1016/j.stem.2013.06.015.
Numerous studies have shown that the bone marrow (BM) niche plays a key role in mouse hematopoietic stem cell (HSC) function and involves contributions from a broad array of cell types. However, the composition and role of the human BM HSC niche have not been investigated. Here, using human bone biopsy specimens, we provide evidence of HSC propensity to localize to endosteal regions of the trabecular bone area (TBA). Through functional xenograft transplantation, we found that human HSCs localizing to the TBA have superior regenerative and self-renewal capacity and are molecularly distinct from those localizing to the long bone area (LBA). In addition, osteoblasts in the TBA possess unique characteristics and express a key network of factors that regulate TBA- versus LBA-localized human HSCs in vivo. Our study reveals that BM localization and architecture play a critical role in defining the functional and molecular properties of human HSCs.
大量研究表明，骨髓（BM）龛在小鼠造血干细胞（HSC）功能中起着关键作用，涉及多种细胞类型的贡献。然而，人类 BM HSC 龛的组成和作用尚未得到研究。在这里，我们使用人类骨活检标本提供了 HSC 倾向于定位于小梁骨区（TBA）的骨内膜区域的证据。通过功能异种移植移植，我们发现定位于 TBA 的人类 HSC 具有更高的再生和自我更新能力，并且在分子上与定位于长骨区（LBA）的 HSC 不同。此外，TBA 中的成骨细胞具有独特的特征，并表达关键的网络因子，这些因子在体内调节 TBA 与 LBA 定位的人类 HSC。我们的研究揭示了 BM 定位和结构在定义人类 HSC 的功能和分子特性方面起着关键作用。
