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Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche

  1. Author:
    Suh, H. C.
    Ji, M.
    Gooya, J.
    Lee, M.
    Klarmann, K. D.
    Keller, J. R.

  2. Author Address

    Suh, Hyung Chan, Ji, Ming, Gooya, John, Lee, Michael, Klarmann, Kimberly D.; Keller, Jonathan R.] SAIC Frederick Inc, Ctr Canc Res, Natl Canc Inst Frederick, Basic Res Program, Frederick, MD 21702 USA.
    1. Year: 2009
  2. Journal: Blood
    1. 114
    2. 6
    3. Pages: 1186-1195
  4. Type of Article: Article
  1. Abstract:

    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. (Blood. 2009, 114: 1186-1195)

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  2. DOI: 10.1182/blood-2008-09-179788
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