Niizuma Kouta, Morikawa Satoru, Gars Eric, Xiang Jinyi, Matsubara-Takahashi Tomoko, Saito Rei, Takematsu Eri, Wang Yuting, Xu Haojun, Wakimoto Arata, Tan Tze Kai, Kubota Yoshiaki, Chan Charles K F, Weissman Irving L, Nakagawa Taneaki, Wilkinson Adam C, Nakauchi Hiromitsu, Yamamoto Ryo
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.
Stem Cell Reports. 2025 Jan 14;20(1):102374. doi: 10.1016/j.stemcr.2024.11.004. Epub 2024 Dec 12.
Hematopoietic stem cells (HSCs) are crucial for maintaining hematopoietic homeostasis and are localized within distinct bone marrow (BM) niches. While BM niches are often considered similar across different skeletal sites, we discovered that the alveolar BM (al-BM) in the mandible harbors the highest frequency of immunophenotypic HSCs in nine different skeletal sites. Transplantation assays revealed significantly increased engraftment from al-BM compared to femur, tibia, or pelvis BM, likely due to a higher proportion of alveolar HSCs. Moreover, hematopoietic progenitor cells (c-Kit Sca-1 Lin) in al-BM exhibited increased quiescence and reduced apoptosis, indicating superior maintenance and survival characteristics. We also observed an enrichment of mesenchymal stromal cells and skeletal stem cells in al-BM, suggesting a more supportive microenvironment. These findings indicate that al-BM provides a unique microenvironment conducive to higher frequency of HSCs, offering new insights into site-specific hematopoiesis.
造血干细胞(HSCs)对于维持造血稳态至关重要,且定位于不同的骨髓(BM)龛位中。虽然通常认为不同骨骼部位的BM龛位相似,但我们发现下颌骨中的牙槽骨骨髓(al-BM)在九个不同骨骼部位中拥有免疫表型HSCs的最高频率。移植试验显示,与股骨、胫骨或骨盆骨髓相比,al-BM的植入显著增加,这可能是由于牙槽HSCs的比例更高。此外,al-BM中的造血祖细胞(c-Kit Sca-1 Lin)表现出更高的静止状态和更低的凋亡率,表明其具有更好的维持和存活特性。我们还观察到al-BM中间充质基质细胞和骨骼干细胞的富集,这表明其具有更具支持性的微环境。这些发现表明,al-BM提供了一个独特的微环境,有利于更高频率的HSCs存在,为位点特异性造血提供了新的见解。