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- Title
Bmi1 is critical to prevent Ikaros-mediated lymphoid priming in hematopoietic stem cells.
- Authors
Arranz, Lorena; Herrera-Merchan, Antonio; Ligos, Jose Manuel; de Molina, Antonio; Dominguez, Orlando; Gonzalez, Susana
- Abstract
Preservation of hematopoietic hierarchy requires a constant and reciprocal interplay between chromatin-specific epigenetic regulators and lineage-modifying transcription factors. The polycomb member Bmi1 is a key factor in hematopoietic stem cell (HSC) maintenance, but its specific physiological role in subsequent hematopoietic lineage-specific commitments is unclear. Here, we generated conditional Bmi1 knockout (Bmi1-KO) mice. Selective ablation of Bmi1 in the hematopoietic system induced extensive upregulation of Ikaros and concomitant Ikaros-dependent lymphoid-lineage transcriptional priming, which is marked by their loss of H2A ubiquitination and increased H3K4 trimethylation in Bmi1-KO long-term HSCs (LT-HSCs). Removal of Ikaros in Bmi1-null LT-HSCs significantly diminished the hematopoietic defects seen in conditional Bmi1-KO mice. These alterations resulted in recovering the Bmi1-KO exhausted quiescent stem-cell pool, whereas the block in Bmi1-KO lymphoid-progenitor differentiation was rescued, allowing the development of mature lymphoid cells. Together, our results indicate that Ikaros is a critical Bmi1 target in vivo that prevents premature lineage specification of HSCs.
- Publication
Cell cycle (Georgetown, Tex.), 2012, Vol 11, Issue 1, p65
- ISSN
1551-4005
- Publication type
Journal Article
- DOI
10.4161/cc.11.1.18097