C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function

IF 29.5 1区医学 Q1 HEMATOLOGY

Journal of Hematology & Oncology Pub Date : 2025-04-01 DOI:10.1186/s13045-025-01687-1

Óscar Herranz, Pablo Berrocal, Carmen Sicilia-Navarro, Cristina Fernández-Infante, Luis Hernández-Cano, Almudena Porras, Carmen Guerrero

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Abstract

C3G, a Rap1 GEF, promotes megakaryopoiesis and platelet function. Using transgenic and knock-out mouse models targeting C3G in megakaryocytes, we investigated whether C3G also affects the niche function of megakaryocytes during bone marrow (BM) recovery after myeloablation induced by 5-fluorouracil (5-FU), or total body irradiation (TBI) followed by bone marrow transplantation. C3G promoted megakaryocyte maturation and platelet production during recovery, along with increased white and red blood cell counts and enhanced survival of female mice after repeated doses of 5-FU. Additionally, megakaryocytes favored adipocyte differentiation through a C3G-mediated mechanism, likely involving Fgf1. Changes in the number or behavior of BM megakaryocytes and adipocytes influenced the hematopoietic stem cell pool, with C3G promoting its bias towards the myeloid-megakaryocytic lineage in both 5-FU- and TBI-ablated models. Therefore, C3G could be a potential target in therapies aimed at enhancing hematopoiesis in patients undergoing chemotherapy and/or BM transplantation.

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来源期刊

Journal of Hematology & Oncology 医学-血液学

CiteScore

48.10

自引率

2.10%

发文量

169

审稿时长

6-12 weeks

期刊介绍： The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.