학술논문

Identification and Specification of the Mouse Skeletal Stem Cell
Document Type
article
Source
Cell. 160(1-2)
Subject
Medical Biotechnology
Biomedical and Clinical Sciences
Stem Cell Research - Embryonic - Non-Human
Genetics
Stem Cell Research - Nonembryonic - Non-Human
Transplantation
Pediatric
Regenerative Medicine
Stem Cell Research
Stem Cell Research - Nonembryonic - Human
1.1 Normal biological development and functioning
Development of treatments and therapeutic interventions
Underpinning research
5.2 Cellular and gene therapies
2.1 Biological and endogenous factors
Aetiology
Musculoskeletal
Animals
Bone Morphogenetic Proteins
Bone and Bones
Cartilage
Cell Lineage
Crosses
Genetic
Mesenchymal Stem Cells
Mice
Mice
Inbred C57BL
Signal Transduction
Biological Sciences
Medical and Health Sciences
Developmental Biology
Biological sciences
Biomedical and clinical sciences
Language
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.