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Mouse skeletal stem cells identified and characterized
DOI:10.1038/bonekey.2015.54
After crossing Rainbow mice with a strain expressing a tamoxifen-inducible Cre under the promoter for actin, Chan et al. were able to observe the clonal regions present at the bone growth plate, revealing stromal tissue, bone and cartilage but no other tissues.
These tissues are derived in vivo from stem cells that have a restricted lineage and that do not differentiate into fat or muscle.
Eight subpopulations of stem cells were identified and their developmental fates determined. Three gave rise to tissue made up from cartilage, bone and marrow; four developed predominantly into bone with no marrow and only a tiny amount of cartilage; the eighth produce virtually all cartilage with no marrow and minimal bone.
A complex series of experiments led to the identification of a lineage tree of skeletal stem cells and the authors identified factors in the mSSC niche that support and regulate activity and development of the downstream progenitor populations.
Editor’s comment: This elegant study by lineage tracing demonstrated that postnatal mSSC formation and subsequent lineage determination are controlled by regulation of the activities of soluble factors, and that specific combinations of SSC niche factors can induce de novo formation of cartilage or bone even in extraskeletal tissues. These observations can represent a paradigm shift in the therapeutic regeneration of bone and cartilage, and may even extend to the regeneration of bone marrow stroma-dependent hematopoietic system.
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