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Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential
  • Daniel L. Worthley, Columbia University
  • Michael Churchill, Columbia University
  • Jocelyn T. Compton, Columbia University Irving Medical Center
  • Yagnesh Tailor, Columbia University
  • Meenakshi Rao, Columbia University
  • Yiling Si, Columbia University
  • Daniel Levin, Keck School of Medicine of USC
  • Matthew G. Schwartz, Harvard Medical School
  • Aysu Uygur, Harvard Medical School
  • Yoku Hayakawa, Columbia University
  • Stefanie Gross, Columbia University
  • Bernhard W. Renz, Columbia University
  • Wanda Setlik, Columbia University
  • Ashley N. Martinez, Columbia University Irving Medical Center
  • Xiaowei Chen, Columbia University
  • Saqib Nizami, Columbia University Irving Medical Center
  • Heon Goo Lee, Columbia University Irving Medical Center
  • H. Paco Kang, Columbia University Irving Medical Center
  • Jon Michael Caldwell, Columbia University Irving Medical Center
  • Samuel Asfaha, Columbia University
  • C. Benedikt Westphalen, Columbia University
  • Trevor Graham, Barts and The London School of Medicine and Dentistry
  • Guangchun Jin, Columbia University
  • Karan Nagar, Columbia University
  • Hongshan Wang, Columbia University
  • Mazen A. Kheirbek, Columbia University
  • Alka Kolhe, Columbia University
  • Jared Carpenter, Columbia University
  • Mark Glaire, Columbia University
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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).

Citation Information
Daniel L. Worthley, Michael Churchill, Jocelyn T. Compton, Yagnesh Tailor, et al.. "Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential" Cell Vol. 160 Iss. 1-2 (2015) p. 269 - 284
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