NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal

AUTOR(ES)

Zhu, Jiang

FONTE

National Academy of Sciences

RESUMO

Hematopoietic stem cell (HSC) self-renewal and differentiation are influenced through multiple pathways, including homeobox transcription factors, signaling through β-catenin and Notch-1, telomerase, and p27. How these multiple pathways interact and are orchestrated is currently unknown. We now report that NF-Ya, the regulatory and DNA-binding subunit of the trimeric transcription factor NF-Y, plays a central, integrating role in several of these HSC pathways. NF-Ya is preferentially expressed in HSC-enriched bone marrow subpopulations, and NF-Ya mRNA rapidly declines with HSC differentiation. Overexpression of NF-Ya in primitive hematopoietic cells activates the transcription of multiple HOX4 paralogs, as well as Notch-1, LEF-1, and telomerase RNA. HSCs overexpressing NF-Ya are biased toward primitive hematopoiesis in vitro and show strikingly increased in vivo repopulating abilities after single or sequential bone marrow transplantation. Thus, NF-Ya is a potent cellular regulator of HSC self-renewal.

Documentos Relacionados

• c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation
• Cytokine manipulation of primitive human hematopoietic cell self-renewal
• Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal
• Self-renewal of the long-term repopulating stem cell.
• Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells