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 Blood, 6 August 2009, Vol. 114, No. 6, pp. 1186-1195.
Prepublished online as a Blood First Edition Paper on May 28, 2009; DOI 10.1182/blood-2008-09-179788.

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HEMATOPOIESIS AND STEM CELLS

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

Hyung Chan Suh1, Ming Ji1, John Gooya1, Michael Lee1, Kimberly D. Klarmann1, and Jonathan R. Keller1

1 Basic Research Program, SAIC-Frederick Inc, Center For Cancer Research, National Cancer Institute-Frederick, MD

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.


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