title: Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche.
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.
authors.affiliation: Basic Research Program, SAIC-Frederick Inc, Center For Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
authors.forename: Hyung Chan
authors.initials: HC
authors.lastname: Suh
authors.forename: Ming
authors.initials: M
authors.lastname: Ji
authors.forename: John
authors.initials: J
authors.lastname: Gooya
authors.forename: Michael
authors.initials: M
authors.lastname: Lee
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Klarmann
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Keller
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D016207:Cytokines; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1