Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential
By Dan Worthley, Michael Churchill, Jocelyn T. Compton, Y. Tailor, M. Rao, Y. Si, D. Levin, Matthew G. Schwartz, Aysu Uygur, Y. Hayakawa and 41 more. Cell, 2015
599 citations recorded by the source corpus.
The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).
Subfields: Genetics, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/e0b51f9718fc865ba96289a0ab1b2694e74252c5
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Citations in the corpus
- Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration (2017, background): “, 2015), which have been proposed to be one of two distinct skeletogenic stem cell populations contributing to post-natal development of bone (Worthley et al., 2015).”
- Spatially organized multicellular immune hubs in human colorectal cancer (2021, result): “, 2017), most prominently along a distribution similar to that of the muscularis mucosa (Figure S3G), as described previously (Davis et al., 2015; Harnack et al., 2019; Worthley et al., 2015).”