Expression data from human glioma cancer stem cell (CSC) specimens following knockdown of GREM1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52846 | GEO | 2014/06/03
SECONDARY ACCESSION(S): PRJNA230288
REPOSITORIES: GEO
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Project description:CSCs differentially secrete the BMP antagonist Gremlin1 compared to non-stem glioma populations. Knockdown of Gremlin1 decreases CSC proliferation and tumorigenicity, establishing Gremlin1 as an essential effector for CSC maintenance. We used a microarray to determine the gene expression programs that are activated downstream of Gremlin1 that might be responsible for CSC maintenance. Glioma CSC cultures from two distinct patient-derived specimens (528 and 3691) were transduced with lentivirus expressing non-targeting scrambled shRNA or one of two distinct Gremlin1 shRNAs (shGrem1_485 and shGrem1_2456) for 72 hours (total of six samples). RNA was extracted for array hybridization.
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Project description: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.
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