| Literature DB >> 25594184 |
Charles K F Chan1, Eun Young Seo2, James Y Chen3, David Lo2, Adrian McArdle2, Rahul Sinha4, Ruth Tevlin2, Jun Seita4, Justin Vincent-Tompkins3, Taylor Wearda2, Wan-Jin Lu4, Kshemendra Senarath-Yapa5, Michael T Chung5, Owen Marecic5, Misha Tran5, Kelley S Yan6, Rosalynd Upton3, Graham G Walmsley2, Andrew S Lee3, Debashis Sahoo7, Calvin J Kuo6, Irving L Weissman4, Michael T Longaker8.
Abstract
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.Entities:
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Year: 2015 PMID： 25594184 PMCID： PMC4297645 DOI： 10.1016/j.cell.2014.12.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850