Cell non-autonomous function of Id1 in the hematopoietic progenitor cell niche

  • Suh H
  • Ji M
  • Gooya J
 et al. 
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Abstract

Development of hematopoietic stem cells (HSC) and their immediate progeny is maintained by the interaction with cells in the microenvironment. We found that hematopoiesis was dysregulated in Id1-/- mice. While the frequency of HSC in Id1-/- bone marrow (BM) was increased, their total numbers remained unchanged due to decreased BM cellularity. Also, the ability of Id1-/- HSC 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 non-autonomous mechanisms for the increased cycling. Id1-/- HSC developed normally when transplanted into Id1+/+ mice, while the development of Id1+/+ HSC was impaired in Id1-/- transplant recipients, and reproduced the hematologic features of Id1-/- mice, indicating that the Id1-/- microenvironment can not 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 HSC.

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Authors

  • H C Suh

  • M Ji

  • J Gooya

  • M Lee

  • K D Klarmann

  • J R Keller

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