Experimental hematology · 2025
FOXP1 contributes to murine hematopoietic stem cell functionality.
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Levavasseur Françoise, Oussous Samia, Framarini Alessandro, Boussaid Ismael, Gou Panhong, Tuerdi Zubaidan, Boueya Iman Litchy, Hoffner Helyette, De Almeida Marta, Gall Morgane Le, Tucker Haley, Giraudier Stéphane, Bouscary Didier, Fontenay Michaela, Passaro Diana, Dusanter-Fourt Isabelle, Lauret Evelyne
Аннотация
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.