the endoplasmic reticulum chaperone protein grp94 is required for maintaining hematopoietic stem cell interactions with the adult bone marrow niche内质网伴侣蛋白grp94需要维护与成人骨髓造血干细胞的相互作用.pdf

The Endoplasmic Reticulum Chaperone Protein GRP94 Is Required for Maintaining Hematopoietic Stem Cell Interactions with the Adult Bone Marrow Niche 1 2 3 1 1 1 3 Biquan Luo , Ben S. Lam , Sung Hyung Lee , Shiuan Wey , Hui Zhou , Miao Wang , Si-Yi Chen , 2 1 Gregor B. Adams , Amy S. Lee * 1 Department of Biochemistry and Molecular Biology and the USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America, 2 Department of Cell and Neurobiology, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America, 3 Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America Abstract Hematopoietic stem cell (HSC) homeostasis in the adult bone marrow (BM) is regulated by both intrinsic gene expression products and interactions with extrinsic factors in the HSC niche. GRP94, an endoplasmic reticulum chaperone, has been reported to be essential for the expression of specific integrins and to selectively regulate early T and B lymphopoiesis. In GRP94 deficient BM chimeras, multipotent hematopoietic progenitors persisted and even increased, however, the mechanism is not well understood. Here we employed a conditional knockout (KO) strategy to acutely eliminate GRP94 in the hematopoietic system. We observed an increase in HSCs and granulocyte-monocyte progenitors in the Grp94 KO BM, correlating with an increased number of colony forming units. Cell cycle a