Identification and Specification of the Mouse Skeletal Stem Cell

被引:581
作者
Chan, Charles K. F. [1 ,5 ]
Seo, Eun Young [1 ,5 ]
Chen, James Y. [2 ,3 ]
Lo, David [1 ,5 ]
McArdle, Adrian [1 ,5 ]
Sinha, Rahul [2 ,3 ,5 ]
Tevlin, Ruth [1 ,5 ]
Seita, Jun [2 ,3 ,5 ]
Vincent-Tompkins, Justin [2 ,3 ]
Wearda, Taylor [1 ,5 ]
Lu, Wan-Jin [2 ,3 ,5 ]
Senarath-Yapa, Kshemendra [1 ]
Chung, Michael T. [1 ]
Marecic, Owen [1 ]
Tran, Misha [1 ]
Yan, Kelley S. [4 ]
Upton, Rosalynd [2 ,3 ]
Walmsley, Graham G. [1 ,5 ]
Lee, Andrew S. [2 ,3 ]
Sahoo, Debashis [2 ,3 ,5 ,6 ]
Kuo, Calvin J. [4 ]
Weissman, Irving L. [2 ,3 ,5 ]
Longaker, Michael T. [1 ,5 ]
机构
[1] Stanford Univ, Dept Surg, Palo Alto, CA 94305 USA
[2] Stanford Univ, Dept Pathol, Palo Alto, CA 94305 USA
[3] Stanford Univ, Dept Dev Biol, Palo Alto, CA 94305 USA
[4] Stanford Univ, Stanford Canc Inst, Palo Alto, CA 94305 USA
[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94305 USA
[6] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
HEMATOPOIETIC NICHE; BONE; CARTILAGE; GROWTH; ANGIOGENESIS; LINEAGE; VEGF; OSTEOARTHRITIS; REGENERATION; OSSIFICATION;
D O I
10.1016/j.cell.2014.12.002
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
How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.
引用
收藏
页码:285 / 298
页数:14
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