FOXP1 contributes to murine hematopoietic stem cell functionality
Transcription factor forkhead box P1 (FOXP1) is a key regulator of immune cell functions. We have shown that FOXP1 contributes to the expansion of human hematopoietic stem/progenitor cell (HSPC) and acute myeloid leukemia cells. Here, we investigated the role of FOXP1 in early adult mouse hematopoiesis in vivo. We showed that loss of hematopoietic-specific FOXP1 expression leads to attrition of the hematopoietic stem cell (HSC) and multipotent progenitor (MPP)-1 compartment in parallel with enhancement of myeloid-biased MPP3 in adult bone marrow and fetal liver. Transplantation experiments confirmed that FOXP1-deficient bone marrow had an intrinsic reduced HSC compartment. FOXP1-deficient MPP compartments also showed enhanced proliferation with G0 phase reduction. Transcriptome analyses revealed that FOXP1-deficient HSC exhibited reduced stemness and enhanced expression of cell proliferation pathways. Thus, our current results revealed that FOXP1 plays a critical role in early murine hematopoiesis by maintaining HSCs, limiting the expansion of all MPP compartments, and restricting early myeloid commitment in vivo.
Authors
- Samia Oussous (ORCID: https://orcid.org/0000-0001-7741-2976)
- Evelyne Lauret (ORCID: https://orcid.org/0000-0003-4643-6857)
- Ismael Boussaïd (ORCID: https://orcid.org/0000-0002-1839-8411)
- Françoise Levavasseur (ORCID: https://orcid.org/0000-0001-6775-4542)
- Panhong Gou (ORCID: https://orcid.org/0000-0001-9408-5663)
- Zubaidan Tuerdi (ORCID: https://orcid.org/0009-0002-8271-3428)
- Haley O. Tucker (ORCID: https://orcid.org/0000-0001-7735-2862)
- Didier Bouscary (ORCID: https://orcid.org/0000-0003-3654-5064)
- Michaëla Fontenay (ORCID: https://orcid.org/0000-0002-5492-6349)
- Morgane Le Gall (ORCID: https://orcid.org/0000-0002-4935-7065)
- Diana Passaro (ORCID: https://orcid.org/0000-0002-2488-3755)
- Stéphane Giraudier (ORCID: https://orcid.org/0000-0002-1817-2236)
- Isabelle Dusanter‐Fourt (ORCID: https://orcid.org/0000-0002-9286-1021)
- Marta de Almeida
- Iman Litchy Boueya
- Alessandro Framarini
- Helyette Hoffner
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Hôpital Cochin (FR)
- Institut Cochin (FR)
- Hôpital Saint-Louis (FR)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Experimental Hematology
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1016/j.exphem.2025.104815
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Université de Paris