title: Cav-1 deletion impaired hematopoietic stem cell function.
abstract: A tightly controlled balance between hematopoietic stem and progenitor cell compartments is required to maintain normal blood cell homeostasis throughout life, and this balance is regulated by intrinsic and extrinsic cellular factors. Cav-1 is a 22-kDa protein that is located in plasma membrane invaginations and is implicated in regulating neural stem cell and embryonic stem cell proliferation. However, the role of Cav-1 in hematopoietic stem cell (HSC) function is largely unknown. In this study, we used Cav-1(-/-) mice to investigate the role of Cav-1 in HSCs function during aging. The results showed that Cav-1(-/-) mice displayed a decreased percentage of B cells and an increased percentage of M cells in the bone marrow and peripheral blood, and these changes were due to an increased number of HSCs. FACS analysis showed that the numbers of Lin(-)Sca1(+)c-kit(+) cells (LSKs), long-term HSCs (LT-HSCs), short-term HSCs and multipotent progenitors were increased in Cav-1(-/-) mice compared with Cav-1(+/+) mice, and this increase became more pronounced with aging. An in vitro clonogenic assay showed that LT-HSCs from Cav-1(-/-) mice had reduced ability to self-renew. Consistently, an in vivo competitive transplantation assay showed that Cav-1(-/-) mice failed to reconstitute hematopoiesis. Moreover, a Cav-1 deletion disrupted the quiescence of LSKs and promoted cell cycle progression through G2/M phase. In addition, we found that Cav-1 deletion impaired the ability of HSCs to differentiate into mature blood cells. Taken together, these data suggest that Cav-1-deficient cells impaired HSCs quiescence and induced environmental alterations, which limited HSCs self-renewal and function.
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: L
authors.initials: L
authors.lastname: Bai
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: G
authors.initials: G
authors.lastname: Shi
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: F
authors.initials: F
authors.lastname: Guan
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 310036, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 310036, China.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Cong
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D051242:Caveolin 1 / Q000172:deficiency / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D051242:Caveolin 1