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They are capable of self-renewal and multilineage differentiation into osteoblasts, chondrocytes, adipocytes, and stromal cells. Importantly, these bone marrow SSCs localize in the perivascular region and highly express hematopoietic growth factors to create the hematopoietic stem cell (HSC) niche. Thus, bone marrow SSCs play pivotal roles in orchestrating osteogenesis and hematopoiesis. Besides the bone marrow, recent studies have uncovered diverse SSC populations in the growth plate, perichondrium, periosteum, and calvarial suture at different developmental stages, which exhibit distinct differentiation potential under homeostatic and stress conditions. Therefore, the current consensus is that a panel of region-specific SSCs collaborate to regulate skeletal development, maintenance, and regeneration. Here, we will summarize recent advances of SSCs in long bones and calvaria, with a special emphasis on the evolving concept and methodology in the field. We will also look into the future of this fascinating research area that may ultimately lead to effective treatment of skeletal disorders.<\/jats:p>","DOI":"10.1093\/lifemedi\/lnac038","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T21:24:10Z","timestamp":1663190650000},"page":"294-306","source":"Crossref","is-referenced-by-count":14,"title":["Skeletal stem cells: a game changer of skeletal biology and regenerative medicine?"],"prefix":"10.1093","volume":"1","author":[{"given":"Qiaoling","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ding","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine and Department of Microbiology and Immunology, Columbia University Irving Medical Center , New York, NY 10032 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yue","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"},{"name":"Shanghai Institute of Stem Cell Research and Clinical Translation , Shanghai 200120 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"2023021814184828300_","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.tem.2009.02.001","article-title":"Bone as an endocrine 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