C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function
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-fluo...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-025-01687-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850265842093129728 |
|---|---|
| author | Óscar Herranz Pablo Berrocal Carmen Sicilia-Navarro Cristina Fernández-Infante Luis Hernández-Cano Almudena Porras Carmen Guerrero |
| author_facet | Óscar Herranz Pablo Berrocal Carmen Sicilia-Navarro Cristina Fernández-Infante Luis Hernández-Cano Almudena Porras Carmen Guerrero |
| author_sort | Óscar Herranz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-129f2b034b6f420db8586ec82ef9c7a7 |
| institution | OA Journals |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-129f2b034b6f420db8586ec82ef9c7a72025-08-20T01:54:19ZengBMCJournal of Hematology & Oncology1756-87222025-04-0118112010.1186/s13045-025-01687-1C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche functionÓscar Herranz0Pablo Berrocal1Carmen Sicilia-Navarro2Cristina Fernández-Infante3Luis Hernández-Cano4Almudena Porras5Carmen Guerrero6Centro de Investigación del Cáncer (CIC), USAL-CSICCentro de Investigación del Cáncer (CIC), USAL-CSICCentro de Investigación del Cáncer (CIC), USAL-CSICCentro de Investigación del Cáncer (CIC), USAL-CSICCentro de Investigación del Cáncer (CIC), USAL-CSICDepartamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de MadridCentro de Investigación del Cáncer (CIC), USAL-CSICAbstract 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.https://doi.org/10.1186/s13045-025-01687-1Rapgef1MegakaryocyteBone marrow nicheMyeloablationAdipocyteHematopoietic stem cell |
| spellingShingle | Óscar Herranz Pablo Berrocal Carmen Sicilia-Navarro Cristina Fernández-Infante Luis Hernández-Cano Almudena Porras Carmen Guerrero C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function Journal of Hematology & Oncology Rapgef1 Megakaryocyte Bone marrow niche Myeloablation Adipocyte Hematopoietic stem cell |
| title | C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| title_full | C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| title_fullStr | C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| title_full_unstemmed | C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| title_short | C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| title_sort | c3g promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function |
| topic | Rapgef1 Megakaryocyte Bone marrow niche Myeloablation Adipocyte Hematopoietic stem cell |
| url | https://doi.org/10.1186/s13045-025-01687-1 |
| work_keys_str_mv | AT oscarherranz c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT pabloberrocal c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT carmensicilianavarro c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT cristinafernandezinfante c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT luishernandezcano c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT almudenaporras c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction AT carmenguerrero c3gpromotesbonemarrowadipocyteexpansionandhematopoieticregenerationaftermyeloablationbyenhancingmegakaryocytenichefunction |