Identification and specification of the mouse skeletal stem cell

Charles K.F. Chan; Eun Young Seo; James Y. Chen; David Lo; Adrian McArdle; Rahul Sinha; Ruth Tevlin; Jun Seita; Justin Vincent-Tompkins; Taylor Wearda; Wan Jin Lu; Kshemendra Senarath-Yapa; Michael T. Chung; Owen Marecic; Misha Tran; Kelley S. Yan; Rosalynd Upton; Graham G. Walmsley; Andrew S. Lee; Debashis Sahoo; Calvin J. Kuo; Irving L. Weissman; Michael T. Longaker

doi:10.1016/j.cell.2014.12.002

Identification and specification of the mouse skeletal stem cell

Charles K.F. Chan
, Eun Young Seo
, James Y. Chen
, David Lo
, Adrian McArdle
, Rahul Sinha
, Ruth Tevlin
, Jun Seita
, Justin Vincent-Tompkins
, Taylor Wearda
, Wan Jin Lu
, Kshemendra Senarath-Yapa
, Michael T. Chung
, Owen Marecic
, Misha Tran
, Kelley S. Yan
, Rosalynd Upton
, Graham G. Walmsley
, Andrew S. Lee
, Debashis Sahoo

Calvin J. Kuo, Irving L. Weissman, Michael T. Longaker

Research output: Contribution to journal › Article › peer-review

625 Scopus citations

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.

Original language	English
Pages (from-to)	285-298
Number of pages	14
Journal	Cell
Volume	160
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cell.2014.12.002
State	Published - Jan 15 2015

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Chan, C. K. F., Seo, E. Y., Chen, J. Y., Lo, D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T., Lu, W. J., Senarath-Yapa, K., Chung, M. T., Marecic, O., Tran, M., Yan, K. S., Upton, R., Walmsley, G. G., Lee, A. S., ... Longaker, M. T. (2015). Identification and specification of the mouse skeletal stem cell. Cell, 160(1-2), 285-298. https://doi.org/10.1016/j.cell.2014.12.002

@article{08b286fee476419eb768d60de5ae6e96,

title = "Identification and specification of the mouse skeletal stem cell",

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.",

author = "Chan, \{Charles K.F.\} and Seo, \{Eun Young\} and Chen, \{James Y.\} and David Lo and Adrian McArdle and Rahul Sinha and Ruth Tevlin and Jun Seita and Justin Vincent-Tompkins and Taylor Wearda and Lu, \{Wan Jin\} and Kshemendra Senarath-Yapa and Chung, \{Michael T.\} and Owen Marecic and Misha Tran and Yan, \{Kelley S.\} and Rosalynd Upton and Walmsley, \{Graham G.\} and Lee, \{Andrew S.\} and Debashis Sahoo and Kuo, \{Calvin J.\} and Weissman, \{Irving L.\} and Longaker, \{Michael T.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.cell.2014.12.002",

language = "English",

volume = "160",

pages = "285--298",

journal = "Cell",

issn = "0092-8674",

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Chan, CKF, Seo, EY, Chen, JY, Lo, D, McArdle, A, Sinha, R, Tevlin, R, Seita, J, Vincent-Tompkins, J, Wearda, T, Lu, WJ, Senarath-Yapa, K, Chung, MT, Marecic, O, Tran, M, Yan, KS, Upton, R, Walmsley, GG, Lee, AS, Sahoo, D, Kuo, CJ, Weissman, IL & Longaker, MT 2015, 'Identification and specification of the mouse skeletal stem cell', Cell, vol. 160, no. 1-2, pp. 285-298. https://doi.org/10.1016/j.cell.2014.12.002

TY - JOUR

T1 - Identification and specification of the mouse skeletal stem cell

AU - Chan, Charles K.F.

AU - Seo, Eun Young

AU - Chen, James Y.

AU - Lo, David

AU - McArdle, Adrian

AU - Sinha, Rahul

AU - Tevlin, Ruth

AU - Seita, Jun

AU - Vincent-Tompkins, Justin

AU - Wearda, Taylor

AU - Lu, Wan Jin

AU - Senarath-Yapa, Kshemendra

AU - Chung, Michael T.

AU - Marecic, Owen

AU - Tran, Misha

AU - Yan, Kelley S.

AU - Upton, Rosalynd

AU - Walmsley, Graham G.

AU - Lee, Andrew S.

AU - Sahoo, Debashis

AU - Kuo, Calvin J.

AU - Weissman, Irving L.

AU - Longaker, Michael T.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84921000919

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DO - 10.1016/j.cell.2014.12.002

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AN - SCOPUS:84921000919

SN - 0092-8674

VL - 160

SP - 285

EP - 298

JO - Cell

JF - Cell

IS - 1-2

ER -

Identification and specification of the mouse skeletal stem cell

Abstract

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