Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation
Takao Yogo,
Hans Jiro Becker,
Takaharu Kimura,
Satoshi Iwano,
Takahiro Kuchimaru,
Atsushi Miyawaki,
Tomomasa Yokomizo,
Toshio Suda,
Atsushi Iwama,
Satoshi Yamazaki
Affiliations
Takao Yogo
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; Corresponding author
Hans Jiro Becker
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
Takaharu Kimura
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
Satoshi Iwano
Institute for Tenure Track Promotion, University of Miyazaki, Miyazaki, Japan
Takahiro Kuchimaru
Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan
Atsushi Miyawaki
Laboratory for Cell Function Dynamics, RIKEN Center for Brain Science, RIKEN, Saitama, Japan
Tomomasa Yokomizo
Department of Microscopic and Developmental Anatomy, Tokyo Women’s Medical University, Tokyo, Japan
Toshio Suda
International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan; Stem Cell Biology Institute of Hematology, Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Atsushi Iwama
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Satoshi Yamazaki
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; Laboratory for Stem Cell Therapy, Faculty of Medicine, Tsukuba University, Ibaraki, Japan; Corresponding author
Summary: 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.
