Yogo Takao, Becker Hans Jiro, Kimura Takaharu, Iwano Satoshi, Kuchimaru Takahiro, Miyawaki Atsushi, Yokomizo Tomomasa, Suda Toshio, Iwama Atsushi, Yamazaki Satoshi
Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Cell Rep. 2025 Feb 25;44(2):115241. doi: 10.1016/j.celrep.2025.115241. Epub 2025 Jan 25.
Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery. Here, we uncovered the spatiotemporal dynamics of early active hematopoiesis, "hematopoietic cell inflation," using a highly sensitive in vivo imaging system. Hematopoietic cell inflation occurs in three peaks in the spleen after transplantation, with common myeloid progenitors (CMPs), notably characterized by HSC-like signatures, playing a central role. Leveraging these findings, we developed expanded CMPs (exCMPs), which exhibit a gene expression pattern that selectively proliferates in the spleen and promotes hematopoietic expansion. Moreover, universal exCMPs supported early hematopoiesis in allogeneic transplantation. Human universal exCMPs have the potential to be a viable therapeutic enhancement for all HSC transplant patients.
造血干细胞（HSCs）具有再生整个造血系统的能力。然而，移植后早期阶段精确的造血干细胞动态仍不明确。临床上，移植后初期的造血过程至关重要，因此需要采取策略来加速造血恢复。在此，我们使用高度灵敏的体内成像系统揭示了早期活跃造血的时空动态，即“造血细胞膨胀”。造血细胞膨胀在移植后脾脏中出现三个峰值，普通髓系祖细胞（CMPs）发挥核心作用，其显著特征是具有类似造血干细胞的特征。利用这些发现，我们开发了扩增的CMPs（exCMPs），其表现出一种在脾脏中选择性增殖并促进造血扩张的基因表达模式。此外，通用exCMPs支持异基因移植中的早期造血。人类通用exCMPs有可能成为所有造血干细胞移植患者可行的治疗增强手段。
