Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche
AUTOR(ES)
Suh, Hyung Chan
FONTE
American Society of Hematology
RESUMO
Development of hematopoietic stem cells (HSCs) and their immediate progeny is maintained by the interaction with cells in the microenvironment. We found that hematopoiesis was dysregulated in Id1−/− mice. Although the frequency of HSCs in Id1−/− bone marrow was increased, their total numbers remained unchanged as the result of decreased bone marrow cellularity. In addition, the ability of Id1−/− HSCs to self-renew was normal, suggesting Id1 does not affect HSC function. Id1−/− progenitors showed increased cycling in vivo but not in vitro, suggesting cell nonautonomous mechanisms for the increased cycling. Id1−/− HSCs developed normally when transplanted into Id1+/+ mice, whereas the development of Id1+/+ HSCs was impaired in Id1−/− recipients undergoing transplantation and reproduced the hematologic features of Id1−/− mice, indicating that the Id1−/− microenvironment cannot support normal hematopoietic development. Id1−/− stromal cells showed altered production of cytokines in vitro, and cytokine levels were deregulated in vivo, which could account for the Id1−/− hematopoietic phenotypes. Thus, Id1 is required for regulating the hematopoietic progenitor cell niche but is dispensable for maintaining HSCs.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2723014Documentos Relacionados
- Cell-nonautonomous function of the retinoblastoma tumour suppressor protein: new interpretations of old phenotypes
- A novel enhancer, the pro-B enhancer, regulates Id1 gene expression in progenitor B cells.
- Massive Apoptosis of Thymocytes in T-Cell-Deficient Id1 Transgenic Mice
- Hyperresponse to T-Cell Receptor Signaling and Apoptosis of Id1 Transgenic Thymocytes
- Regulation of the pro-B-cell-specific enhancer of the Id1 gene involves the C/EBP family of proteins.