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Stem Cell Genetics and Genomics |
1 Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, Bethesda, Maryland; Musculoskeletal Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
* To whom correspondence should be addressed. E-mail: tuanr{at}mail.nih.gov.
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Abstract |
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Adult human mesenchymal stem cells (hMSCs) possess multilineage differentiation potential, and differentiated hMSCs have recently been shown to have the ability to transdifferentiate into other lineages. However, the molecular signature of hMSCs is not well known, and the mechanisms regulating their self-renewal, differentiation, and transdifferentiation are not completely understood. In this study, we demonstrate that fully differentiated hMSCs could dedifferentiate, a likely critical step for transdifferentiation. By comparing the global gene expression profiles of undifferentiated, differentiated, and dedifferentiation cells in three mesenchymal lineages (osteogenesis, chondrogenesis, and adipogenesis), we identified a number of "stemness" and "differentiation" genes that might be essential to maintain adult stem cell multipotency as well as to drive lineage specific commitment. These genes include those that encode cell surface molecules as well as components of signaling pathways. These genes may be valuable for developing methods to isolate, enrich, and purify homogeneous population of hMSCs, and/or maintain and propagate hMSCs as well as guide or regulate their differentiation for gene and cell-based therapy. Using siRNA gene inactivation, we demonstrate that five genes (AFAP, FZD7, DKK3, PTPRF, and RAB3B) promote cell survival without altering cell proliferation, as well as exhibit different effects on the commitment of hMSCs into multiple mesenchymal lineages.
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