MAFB regulates hematopoietic stem cell proliferation and maintenance

MAFB, a transcription factor of the large Maf family, is expressed in both fetal liver (FL) and bone marrow (BM) hematopoietic stem cells (HSCs). However, its stage-specific roles remain elusive. Here, we reveal that MAFB plays distinct roles in FL and BM HSCs. Using Mafb-deficient and Mafb-GFP knock-in mouse models, we demonstrate that Mafb deletion enhances proliferation, cell cycle entry, and myeloid differentiation of FL HSCs, leading to enhanced chimerism rate in transplantation assays. However, Mafb-deficient BM HSCs exhibit impaired long-term reconstitution and progressive exhaustion, supported by serial transplantation and reduced colony-forming capacity. HSCs from Mafb^f/f::Tie2-Cre mouse (Mafb cKO) further revealed a significant decline in long-term HSC (LT-HSC) populations and multilineage differentiation potential. Together, our findings suggest a stage-dependent role of MAFB as a regulator of HSC proliferation during fetal development and a critical factor for HSC maintenance during adulthood, providing insights into the stage-specific regulation of HSC function linked to cell cycle control and long-term repopulation capacity.