sirolimus and 2-2-bis(4-glycidyloxyphenyl)propane

Myelotoxic injury, such as chemotherapeutic agents and ionizing radiation, unlocks the vigorous power of hematopoietic stem cells (HSCs) to replenish the hematopoietic system, making quiescent HSCs enter the cell cycle. Considering that both HSC-intrinsic and -extrinsic mechanisms enforce quiescence of HSCs, the drastic change in bone marrow (BM) environment after injury, represented by massive expansion of BM adipocytes, might trigger HSC activation. BM adipocytes, the major cellular component in the ablated marrow, however, reportedly suppress proliferation of hematopoietic cells, which may indicate the BM adipocytogenesis is an irrational response of injured organism. Given that adipose tissue is an endocrine organ with pleiotropic functions, we hypothesized that adipocyte-derived factors, especially adiponectin, an anti-inflammatory adipokine involved in regulation of granulopoiesis, are implicated in HSC activation. Myeloablative intervention increased BM adiponectin by multiple mechanisms, including adipocyte expansion and increased diffusion from the blood. Adiponectin-null (Adipoq

Topics: Adiponectin; Animals; Benzhydryl Compounds; Bone Marrow; Bone Marrow Transplantation; Cyclophosphamide; Cytarabine; Epoxy Compounds; Fluorouracil; Gene Expression Regulation; Hematopoiesis; Hematopoietic Stem Cells; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Knockout; Myeloablative Agonists; Poly I-C; Signal Transduction; Sirolimus; Whole-Body Irradiation