Unknown,Transcriptomics,Genomics,Proteomics

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Differential expression of mouse Grem1+ Vs. Grem1- bone-marrow cells


ABSTRACT: The gene expression of bone marrow cells of mice enriched for Gremlin1 vs control was measured (n=3). It is not known if endogenous adult mesenchymal stem cells (MSCs) exist.Following culture,perisinusoidal mesenchymal cells can clonally recapitulate the skeletal microenvironment, but this fails to confirm their endogenous lineage repertoire. Multipotential MSCs in vitro may be fate-restricted in vivo and specific perisinusoidal recombination does not trace bone or cartilage Reconciling in vitro MSCs with their in vivo potential has been challenging and remains untested outside of the bone. We prove that expression of the bone morphogenetic protein (BMP)-antagonist gremlin 1 (Grem1) identifies a population of self-renewing, multipotent bone, cartilage and stromal-primed MSCs in both health and healing that are completely distinct from the established Nes-GFP niche-supporting mesenchymal cells. Grem1 recombination also identifies small intestinal MSCs (siMSCs) that can be transplanted and clonally trace the self-renewing, multilineage periepithelial mesenchymal sheath. Our findings prove the existence of adult MSCs that are regionally and functionally distinct from perisinusoidal Nes-GFP cells. We also established that the mesenchyme undergoes ordered turnover outside of the bone and may help to preserve regional niches. Grem1 MSCs provide a new focus for investigating mesenchymal renewal and repair. a.Adult (6-8 weeks) Grem1;TdTomato mice were induced by oral tamoxifen and their bone marrow harvested by digestion sorted for Non-recombined CD45/CD31/Ter-119 triple negative bone marrow cells (n=3). b.Adult (6-8 weeks) Grem1;TdTomato mice were induced by oral tamoxifen and their bone marrow harvested by digestion sorted for Grem1 (n=3). Same mice as in a so that samples are matched.

ORGANISM(S): Mus musculus

SUBMITTER: Timothy Wang 

PROVIDER: E-GEOD-57729 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

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

Cell 20150101 1-2


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.  ...[more]

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