Yamashita Erika, Hashimoto Soichiro, Abe Hiroaki, Sudo Takao, Okuzaki Daisuke, Okawa Toshiya, Ishii Masaru
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, The University of Osaka, Osaka, Japan.
WPI-Immunology Frontier Research Center, The University of Osaka, Osaka, Japan.
FASEB J. 2025 Sep 15;39(17):e71022. doi: 10.1096/fj.202500885R.
In bone marrow, cell numbers are balanced between production and loss. After chemotherapy, blood cell counts decrease initially but later recover as hematopoietic progenitor cells expand, although the mechanisms underlying this recovery are still unclear. We investigated the influence of red blood cells (RBCs) on hematopoietic stem cell (HSC) function during bone marrow recovery. Following chemotherapy, RBC concentrations in bone marrow peaked on day 5 posttreatment, coinciding with the recovery of hematopoiesis. Coculture of HSCs with RBCs resulted in a significant increase in hematopoiesis. Direct contact between RBCs and HSCs was essential for enhancement of hematopoiesis, and HSCs precultured with RBCs resulted in greater numbers of donor-derived mature hematopoietic cells after transplantation. RNA-sequencing analysis showed that Hes1 was the most significantly upregulated transcription factor in RBC coculture, and the response to RBC-induced hematopoiesis of Hes1-deficient HSCs was reduced. These findings imply a role of RBCs and Hes1 in the enhancement of hematopoietic recovery following bone marrow stress.
在骨髓中，细胞数量在生成与损耗之间保持平衡。化疗后，血细胞计数最初会下降，但随后随着造血祖细胞的扩增而恢复，尽管这种恢复的潜在机制仍不清楚。我们研究了红细胞（RBC）在骨髓恢复过程中对造血干细胞（HSC）功能的影响。化疗后，骨髓中的红细胞浓度在治疗后第5天达到峰值，与造血恢复同时发生。造血干细胞与红细胞共培养导致造血显著增加。红细胞与造血干细胞之间的直接接触对于增强造血至关重要，并且用红细胞预培养的造血干细胞在移植后产生了更多供体来源的成熟造血细胞。RNA测序分析表明，Hes1是红细胞共培养中上调最显著的转录因子，并且Hes1缺陷型造血干细胞对红细胞诱导的造血反应降低。这些发现表明红细胞和Hes1在骨髓应激后增强造血恢复中发挥作用。
