Progenitor Effect in the spleen drives early recovery via Universal Hematopoietic Cell Inflation

Hematopoietic stem cells (HSC) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remains 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（Hematopoietic stem cells, HSC）具备重建整个造血系统的能力。然而，移植后早期阶段造血干细胞的精确动态变化仍是未解之谜。临床实践中，移植后早期的初始造血过程至关重要，亟需开发可加速造血恢复的干预策略。本研究借助高灵敏度活体成像系统，揭示了早期活跃造血的时空动态特征——"造血细胞充盈（Hematopoietic Cell Inflation）"。研究发现，移植后脾脏内的造血细胞充盈现象呈现三个峰值，其中以造血干细胞样特征为显著标志的普通髓系祖细胞（common myeloid progenitors, CMPs）发挥了核心作用。基于上述发现，本团队开发了扩增型普通髓系祖细胞（expanded CMPs, exCMPs），该细胞群展现出可在脾脏中选择性增殖并促进造血扩增的基因表达谱。此外，通用型扩增普通髓系祖细胞可支持异基因移植后的早期造血。人类通用型扩增普通髓系祖细胞有望成为适配所有造血干细胞移植患者的有效治疗增强手段。