Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential

被引：568

作者：

Worthley, Daniel L. ^{[1
,2
,3
,4
,5
]}

Churchill, Michael ^{[1
,2
]}

Compton, Jocelyn T. ^{[6
]}

Tailor, Yagnesh ^{[1
,2
]}

Rao, Meenakshi ^{[7
]}

Si, Yiling ^{[1
,2
]}

Levin, Daniel ^{[8
]}

Schwartz, Matthew G. ^{[9
]}

Uygur, Aysu ^{[9
]}

Hayakawa, Yoku ^{[1
,2
]}

Gross, Stefanie ^{[10
]}

Renz, Bernhard W. ^{[1
,2
]}

Setlik, Wanda ^{[11
]}

Martinez, Ashley N. ^{[6
]}

Chen, Xiaowei ^{[1
,2
]}

Nizami, Saqib ^{[6
]}

Lee, Heon Goo ^{[6
]}

Kang, H. Paco ^{[6
]}

Caldwell, Jon-Michael ^{[6
]}

Asfaha, Samuel ^{[1
,2
]}

Westphalen, C. Benedikt ^{[1
,2
,12
]}

Graham, Trevor ^{[13
]}

Jin, Guangchun ^{[1
,2
]}

Nagar, Karan ^{[1
,2
]}

Wang, Hongshan ^{[1
,2
]}

Kheirbek, Mazen A. ^{[14
]}

Kolhe, Alka ^{[1
,2
]}

Carpenter, Jared ^{[1
,2
]}

Glaire, Mark ^{[1
,2
]}

Nair, Abhinav ^{[1
,2
]}

Renders, Simon ^{[1
,2
]}

Manieri, Nicholas ^{[15
]}

Muthupalani, Sureshkumar ^{[16
]}

Fox, James G. ^{[16
]}

Reichert, Maximilian ^{[16
]}

Giraud, Andrew S. ^{[5
]}

Schwabe, Robert F. ^{[1
,2
]}

Pradere, Jean-Phillipe ^{[1
,2
,18
]}

Walton, Katherine ^{[19
]}

Prakash, Ajay ^{[19
]}

Gumucio, Deborah ^{[19
]}

Rustgi, Anil K. ^{[17
]}

Stappenbeck, Thaddeus S. ^{[15
]}

Friedman, Richard A. ^{[20
,21
]}

Gershon, Michael D. ^{[11
]}

Sims, Peter ^{[22
]}

Grikscheit, Tracy ^{[8
]}

Lee, Francis Y. ^{[6
]}

Karsenty, Gerard ^{[10
]}

Mukherjee, Siddhartha ^{[1
,2
]}

机构：

[1] Columbia Univ, Dept Med, New York, NY 10032 USA

[2] Columbia Univ, Irving Canc Res Ctr, New York, NY 10032 USA

[3] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia

[4] South Australian Hlth & Med Res Inst, Adelaide, SA 5001, Australia

[5] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[6] Columbia Univ, Med Ctr, Dept Orthoped Surg, New York, NY 10032 USA

[7] Columbia Univ, Dept Pediat, New York, NY 10032 USA

[8] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA

[9] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

[10] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[11] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[12] Univ Munich, Univ Hosp Munich, Dept Internal Med 3, D-81377 Munich, Germany

[13] Queen Mary Univ London, Barts & London Sch Med & Dent, Barts Canc Inst, London EC1M 6BQ, England

[14] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[15] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA

[16] MIT, Div Comparat Med, Cambridge, MA 02139 USA

[17] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Div Gastroenterol,Dept Med & Genet, Philadelphia, PA 19104 USA

[18] Univ Toulouse 3, I2MC, INSERM, UMR1048, F-31432 Toulouse, France

[19] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

[20] Columbia Univ, Herbert Irving Comprehens Canc Ctr Biomed Informa, New York, NY 10032 USA

[21] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA

[22] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

来源：

CELL | 2015年 / 160卷 / 1-2期

关键词：

PROGENITOR CELLS; MARROW; DIFFERENTIATION; OSTEOBLAST; LINEAGE; GROWTH; NESTIN; NICHE; MOUSE; FATE;

D O I：

10.1016/j.cell.2014.11.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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).

引用

页码：269 / 284

页数：16

共 40 条

[1]

Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].

Barker, Nick ;

van Es, Johan H. ;

Kuipers, Jeroen ;

Kujala, Pekka ;

van den Born, Maaike ;

Cozijnsen, Miranda ;

Haegebarth, Andrea ;

Korving, Jeroen ;

Begthel, Harry ;

Peters, Peter J. ;

Clevers, Hans .

NATURE, 2007, 449 (7165) :1003-U1

[2]

Nestin-expressing cells in the gut give rise to enteric neurons and glial cells [J].

Belkind-Gerson, J. ;

Carreon-Rodriguez, A. ;

Benedict, L. Andrew ;

Steiger, C. ;

Pieretti, A. ;

Nagy, N. ;

Dietrich, J. ;

Goldstein, A. M. .

NEUROGASTROENTEROLOGY AND MOTILITY, 2013, 25 (01) :61-E7

[3]

A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning [J].

Benazet, Jean-Denis ;

Bischofberger, Mirko ;

Tiecke, Eva ;

Goncalves, Alexandre ;

Martin, James F. ;

Zuniga, Aimee ;

Naef, Felix ;

Zeller, Rolf .

SCIENCE, 2009, 323 (5917) :1050-1053

[4]

The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine [J].

Bianco, Paolo ;

Cao, Xu ;

Frenette, Paul S. ;

Mao, Jeremy J. ;

Robey, Pamela G. ;

Simmons, Paul J. ;

Wang, Cun-Yu .

NATURE MEDICINE, 2013, 19 (01) :35-42

[5]

A perivascular origin for mesenchymal stem cells in multiple human organs [J].

Crisan, Mihaela ;

Yap, Solomon ;

Casteilla, Louis ;

Chen, Chien-Wen ;

Corselli, Mirko ;

Park, Tea Soon ;

Andriolo, Gabriella ;

Sun, Bin ;

Zheng, Bo ;

Zhang, Li ;

Norotte, Cyrille ;

Teng, Pang-Ning ;

Traas, Jeremy ;

Schugar, Rebecca ;

Deasy, Bridget M. ;

Badylak, Stephen ;

Buehring, Hans-Joerg ;

Giacobino, Jean-Paul ;

Lazzari, Lorenza ;

Huard, Johnny ;

Peault, Bruno .

CELL STEM CELL, 2008, 3 (03) :301-313

[6]

Specific Lineage-Priming of Bone Marrow Mesenchymal Stem Cells Provides the Molecular Framework for Their Plasticity [J].

Delorme, Bruno ;

Ringe, Jochen ;

Pontikoglou, Charalampos ;

Gaillard, Julien ;

Langonné, Alain ;

Sensebe, Luc ;

Noel, Daniele ;

Jorgensen, Christian ;

Haeupl, Thomas ;

Charbord, Pierre .

STEM CELLS, 2009, 27 (05) :1142-1151

[7]

Endothelial and perivascular cells maintain haematopoietic stem cells [J].

Ding, Lei ;

Saunders, Thomas L. ;

Enikolopov, Grigori ;

Morrison, Sean J. .

NATURE, 2012, 481 (7382) :457-U65

[8]

Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].

Dominici, M. ;

Le Blanc, K. ;

Mueller, I. ;

Slaper-Cortenbach, I. ;

Marini, F. C. ;

Krause, D. S. ;

Deans, R. J. ;

Keating, A. ;

Prockop, D. J. ;

Horwitz, E. M. .

CYTOTHERAPY, 2006, 8 (04) :315-317

[9]

Experience Dictates Stem Cell Fate in the Adult Hippocampus [J].

Dranovsky, Alex ;

Picchini, Alyssa M. ;

Moadel, Tiffany ;

Sisti, Alexander C. ;

Yamada, Atsushi ;

Kimura, Shioko ;

Leonardo, E. David ;

Hen, Rene .

NEURON, 2011, 70 (05) :908-923

[10]

Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].

Ducy, P ;

Zhang, R ;

Geoffroy, V ;

Ridall, AL ;

Karsenty, G .

CELL, 1997, 89 (05) :747-754

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