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

Blood. 2009 Aug 6;114(6):1186-95. doi: 10.1182/blood-2008-09-179788. Epub 2009 May 28.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow / metabolism*
  • Cell Cycle / physiology*
  • Cytokines / metabolism
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Inhibitor of Differentiation Protein 1 / metabolism*
  • Mice
  • Mice, Knockout
  • Stromal Cells / cytology
  • Stromal Cells / metabolism

Substances

  • Cytokines
  • Idb1 protein, mouse
  • Inhibitor of Differentiation Protein 1