Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential

Daniel L. Worthley; Michael Churchill; Jocelyn T. Compton; Yagnesh Tailor; Meenakshi Rao; Yiling Si; Daniel Levin; Matthew G. Schwartz; Aysu Uygur; Yoku Hayakawa; Stefanie Gross; Bernhard W. Renz; Wanda Setlik; Ashley N. Martinez; Xiaowei Chen; Saqib Nizami; Heon Goo Lee; H. Paco Kang; Jon Michael Caldwell; Samuel Asfaha; C. Benedikt Westphalen; Trevor Graham; Guangchun Jin; Karan Nagar; Hongshan Wang; Mazen A. Kheirbek; Alka Kolhe; Jared Carpenter; Mark Glaire; Abhinav Nair; Simon Renders; Nicholas Manieri; Sureshkumar Muthupalani; James G. Fox; Maximilian Reichert; Andrew S. Giraud; Robert F. Schwabe; Jean Phillipe Pradere; Katherine Walton; Ajay Prakash; Deborah Gumucio; Anil K. Rustgi; Thaddeus S. Stappenbeck; Richard A. Friedman; Michael D. Gershon; Peter Sims; Tracy Grikscheit; Francis Y. Lee; Gerard Karsenty; Siddhartha Mukherjee; Timothy C. Wang

doi:10.1016/j.cell.2014.11.042

Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential

Daniel L. Worthley
, Michael Churchill
, Jocelyn T. Compton
, Yagnesh Tailor
, Meenakshi Rao
, Yiling Si
, Daniel Levin
, Matthew G. Schwartz
, Aysu Uygur
, Yoku Hayakawa
, Stefanie Gross
, Bernhard W. Renz
, Wanda Setlik
, Ashley N. Martinez
, Xiaowei Chen
, Saqib Nizami
, Heon Goo Lee
, H. Paco Kang
, Jon Michael Caldwell
, Samuel Asfaha

C. Benedikt Westphalen, Trevor Graham, Guangchun Jin, Karan Nagar, Hongshan Wang, Mazen A. Kheirbek, Alka Kolhe, Jared Carpenter, Mark Glaire, Abhinav Nair, Simon Renders, Nicholas Manieri, Sureshkumar Muthupalani, James G. Fox, Maximilian Reichert, Andrew S. Giraud, Robert F. Schwabe, Jean Phillipe Pradere, Katherine Walton, Ajay Prakash, Deborah Gumucio, Anil K. Rustgi, Thaddeus S. Stappenbeck, Richard A. Friedman, Michael D. Gershon, Peter Sims, Tracy Grikscheit, Francis Y. Lee, Gerard Karsenty, Siddhartha Mukherjee, Timothy C. Wang

Blood Cancer Program

Research output: Contribution to journal › Article › peer-review

563 Citations (Scopus)

Abstract

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).

Original language	English
Pages (from-to)	269-284
Number of pages	16
Journal	Cell
Volume	160
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cell.2014.11.042
Publication status	Published or Issued - 15 Jan 2015

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2014.11.042

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Worthley, D. L., Churchill, M., Compton, J. T., Tailor, Y., Rao, M., Si, Y., Levin, D., Schwartz, M. G., Uygur, A., Hayakawa, Y., Gross, S., Renz, B. W., Setlik, W., Martinez, A. N., Chen, X., Nizami, S., Lee, H. G., Kang, H. P., Caldwell, J. M., ... Wang, T. C. (2015). Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell, 160(1-2), 269-284. https://doi.org/10.1016/j.cell.2014.11.042

@article{31b05f836de94f3696abe7c980ee8de7,

title = "Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential",

abstract = "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).",

author = "Worthley, \{Daniel L.\} and Michael Churchill and Compton, \{Jocelyn T.\} and Yagnesh Tailor and Meenakshi Rao and Yiling Si and Daniel Levin and Schwartz, \{Matthew G.\} and Aysu Uygur and Yoku Hayakawa and Stefanie Gross and Renz, \{Bernhard W.\} and Wanda Setlik and Martinez, \{Ashley N.\} and Xiaowei Chen and Saqib Nizami and Lee, \{Heon Goo\} and Kang, \{H. Paco\} and Caldwell, \{Jon Michael\} and Samuel Asfaha and Westphalen, \{C. Benedikt\} and Trevor Graham and Guangchun Jin and Karan Nagar and Hongshan Wang and Kheirbek, \{Mazen A.\} and Alka Kolhe and Jared Carpenter and Mark Glaire and Abhinav Nair and Simon Renders and Nicholas Manieri and Sureshkumar Muthupalani and Fox, \{James G.\} and Maximilian Reichert and Giraud, \{Andrew S.\} and Schwabe, \{Robert F.\} and Pradere, \{Jean Phillipe\} and Katherine Walton and Ajay Prakash and Deborah Gumucio and Rustgi, \{Anil K.\} and Stappenbeck, \{Thaddeus S.\} and Friedman, \{Richard A.\} and Gershon, \{Michael D.\} and Peter Sims and Tracy Grikscheit and Lee, \{Francis Y.\} and Gerard Karsenty and Siddhartha Mukherjee and Wang, \{Timothy C.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.cell.2014.11.042",

language = "English",

volume = "160",

pages = "269--284",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1-2",

}

Worthley, DL, Churchill, M, Compton, JT, Tailor, Y, Rao, M, Si, Y, Levin, D, Schwartz, MG, Uygur, A, Hayakawa, Y, Gross, S, Renz, BW, Setlik, W, Martinez, AN, Chen, X, Nizami, S, Lee, HG, Kang, HP, Caldwell, JM, Asfaha, S, Westphalen, CB, Graham, T, Jin, G, Nagar, K, Wang, H, Kheirbek, MA, Kolhe, A, Carpenter, J, Glaire, M, Nair, A, Renders, S, Manieri, N, Muthupalani, S, Fox, JG, Reichert, M, Giraud, AS, Schwabe, RF, Pradere, JP, Walton, K, Prakash, A, Gumucio, D, Rustgi, AK, Stappenbeck, TS, Friedman, RA, Gershon, MD, Sims, P, Grikscheit, T, Lee, FY, Karsenty, G, Mukherjee, S & Wang, TC 2015, 'Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential', Cell, vol. 160, no. 1-2, pp. 269-284. https://doi.org/10.1016/j.cell.2014.11.042

TY - JOUR

T1 - Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential

AU - Worthley, Daniel L.

AU - Churchill, Michael

AU - Compton, Jocelyn T.

AU - Tailor, Yagnesh

AU - Rao, Meenakshi

AU - Si, Yiling

AU - Levin, Daniel

AU - Schwartz, Matthew G.

AU - Uygur, Aysu

AU - Hayakawa, Yoku

AU - Gross, Stefanie

AU - Renz, Bernhard W.

AU - Setlik, Wanda

AU - Martinez, Ashley N.

AU - Chen, Xiaowei

AU - Nizami, Saqib

AU - Lee, Heon Goo

AU - Kang, H. Paco

AU - Caldwell, Jon Michael

AU - Asfaha, Samuel

AU - Westphalen, C. Benedikt

AU - Graham, Trevor

AU - Jin, Guangchun

AU - Nagar, Karan

AU - Wang, Hongshan

AU - Kheirbek, Mazen A.

AU - Kolhe, Alka

AU - Carpenter, Jared

AU - Glaire, Mark

AU - Nair, Abhinav

AU - Renders, Simon

AU - Manieri, Nicholas

AU - Muthupalani, Sureshkumar

AU - Fox, James G.

AU - Reichert, Maximilian

AU - Giraud, Andrew S.

AU - Schwabe, Robert F.

AU - Pradere, Jean Phillipe

AU - Walton, Katherine

AU - Prakash, Ajay

AU - Gumucio, Deborah

AU - Rustgi, Anil K.

AU - Stappenbeck, Thaddeus S.

AU - Friedman, Richard A.

AU - Gershon, Michael D.

AU - Sims, Peter

AU - Grikscheit, Tracy

AU - Lee, Francis Y.

AU - Karsenty, Gerard

AU - Mukherjee, Siddhartha

AU - Wang, Timothy C.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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).

AB - 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).

UR - https://www.scopus.com/pages/publications/84920972443

U2 - 10.1016/j.cell.2014.11.042

DO - 10.1016/j.cell.2014.11.042

M3 - Article

C2 - 25594183

AN - SCOPUS:84920972443

SN - 0092-8674

VL - 160

SP - 269

EP - 284

JO - Cell

JF - Cell

IS - 1-2

ER -

Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential

Abstract

ASJC Scopus subject areas

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