Red Blood Cell-Mediated Enhancement of Hematopoietic Stem Cell Functions via a Hes1-Dependent Pathway

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

The FASEB Journal Pub Date : 2025-09-09 DOI:10.1096/fj.202500885R

Erika Yamashita, Soichiro Hashimoto, Hiroaki Abe, Takao Sudo, Daisuke Okuzaki, Toshiya Okawa, Masaru Ishii

{"title":"Red Blood Cell-Mediated Enhancement of Hematopoietic Stem Cell Functions via a Hes1-Dependent Pathway","authors":"Erika Yamashita, Soichiro Hashimoto, Hiroaki Abe, Takao Sudo, Daisuke Okuzaki, Toshiya Okawa, Masaru Ishii","doi":"10.1096/fj.202500885R","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500885R","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202500885R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

红细胞介导的hes1依赖性造血干细胞功能增强

在骨髓中，细胞数量在产生和损失之间保持平衡。化疗后，血细胞计数最初减少，但后来随着造血祖细胞的增加而恢复，尽管这种恢复的机制尚不清楚。我们研究了骨髓恢复过程中红细胞（rbc）对造血干细胞（HSC）功能的影响。化疗后，骨髓中红细胞浓度在治疗后第5天达到峰值，与造血功能恢复一致。造血干细胞与红细胞共培养可显著增加造血功能。红细胞和造血干细胞之间的直接接触对于增强造血功能是必不可少的，与红细胞一起预培养的造血干细胞在移植后会产生更多的供体来源的成熟造血细胞。rna测序分析显示，在红细胞共培养中，Hes1是最显著上调的转录因子，Hes1缺失的造血干细胞对红细胞诱导的造血反应降低。这些发现暗示了红细胞和Hes1在骨髓应激后促进造血恢复中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

The FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.