A high-throughput siRNA library screen identifies osteogenic suppressors in human mesenchymal stem cells.
Tissue-specific (or adult) stem/progenitor cells are regarded as the source for normal tissue homeostasis and tissue repair. They also provide tremendous promise for regenerative medicine because of their capacity to proliferate and differentiate into a variety of mature cell types. Human mesenchymal stem cells (hMSCs) can differentiate into osteocytes, adipocytes, chondrocytes, muscle cells, and neurons. However, the molecular mechanisms underlying these differentiation processes are poorly understood. We screened a synthetic siRNA library targeting 5,000 human genes to identify the endogenous repressors of osteogenic specification, which when silenced could initiate differentiation of hMSCs into osteoblasts. This screen yielded 53 candidate suppressors, and 12 of those were further confirmed for their dynamic roles in suppressing osteogenic specification in hMSCs. Furthermore, cAMP was identified to play opposing roles in osteogenesis vs. adipogenesis. This study provides a basis for further elucidation of the genetic network controlling osteogenesis and, potentially, the molecular rationale for treating bone diseases.
Zhao
Yuanxiang
Y
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ding
Sheng
S
D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
D034741:RNA, Small Interfering