Identification of the Human Skeletal Stem Cell

被引：447

作者：

Chan, Charles K. F. ^{[1
,2
]}

Gulati, Gunsagar S. ^{[1
,2
]}

Sinha, Rahul ^{[2
]}

Tompkins, Justin Vincent ^{[1
]}

Lopez, Michael ^{[1
]}

Carter, Ava C. ^{[3
]}

Ransom, Ryan C. ^{[1
,2
]}

Reinisch, Andreas ^{[2
]}

Wearda, Taylor ^{[1
]}

Murphy, Matthew ^{[1
]}

Brewer, Rachel E. ^{[1
]}

Koepke, Lauren S. ^{[1
]}

Marecic, Owen ^{[1
]}

Manjunath, Anoop ^{[1
,2
]}

Seo, Eun Young ^{[1
]}

Leavitt, Tripp ^{[1
]}

Lu, Wan-Jin ^{[2
]}

Allison Nguyen ^{[2
]}

Conley, Stephanie D. ^{[2
]}

Salhotra, Ankit ^{[1
]}

Ambrosi, Thomas H. ^{[1
]}

Borrelli, Mimi R. ^{[1
]}

Siebel, Taylor ^{[2
]}

Chan, Karen ^{[2
]}

Schallmoser, Katharina ^{[4
]}

Seita, Jun ^{[5
]}

Sahoo, Debashis ^{[6
,7
]}

Goodnough, Henry ^{[8
]}

Bishop, Julius ^{[8
]}

Gardner, Michael ^{[8
]}

Majeti, Ravindra ^{[9
]}

Wan, Derrick C. ^{[1
]}

Goodman, Stuart ^{[8
]}

Weissman, Irving L. ^{[2
]}

Chang, Howard Y. ^{[3
]}

Longaker, Michael T. ^{[1
,2
]}

机构：

[1] Stanford Med, Dept Surg, Stanford, CA 94305 USA

[2] Stanford Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[3] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[4] Med Univ Graz, Dept Blood Grp Serol & Transfus Med, A-8036 Graz, Austria

[5] RIKEN, Med Sci Innovat Hub Program, Tokyo 1030027, Japan

[6] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA

[7] Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92093 USA

[8] Stanford Med, Dept Orthoped Surg, Stanford, CA 94305 USA

[9] Stanford Med, Dept Med, Div Hematol, Stanford, CA 94305 USA

来源：

CELL | 2018年 / 175卷 / 01期

关键词：

BONE-MARROW; RNA-SEQ; CHROMATIN; REVEALS; GENES; MOUSE;

D O I：

10.1016/j.cell.2018.07.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma canmaintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis.

引用

页码：43 / +

页数：35

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