I-11: Dedifferentiation of Mouse Fibroblast Cells by Chemical Induction
نویسنده
چکیده مقاله:
Induced pluripotent stem cells (iPSCs) generated by ectopic expression of four transcription factors have great promises for regenerative medicine in humans. Since the initial report of iPSCs by viral transfection, ample efforts have been made in the generation of iPSCs through nonviral approaches. Small molecules offer the advantages of low cost without genomic modification and have been used to induce cell reprogramming for lineage transdifferentiation and for maintaining pluripotency of stem cells. Stem cells and cancer cells share many common features, implying that there are similar underlying mechanisms in their development. Chemicals that can activate common pathways in both cancer and stem cells may lead to interesting de-differentiation or trans-differentiation processes. We therefore investigated the possibility of reprogramming somatic cells with carcinogens at non-genotoxic levels. By in silico high-throughput screening of the Sigma-Aldrich’s inventory for cancer research, we identified 16 candidate chemicals and treated B6/129 mouse embryonic fibroblasts (MEFs) at passage 3. The protocol was consisted of a 16-day treatment period followed by 5 days of recovery. From recovery day 2, colonies appeared at an efficiency of 0.02%. These colonies were positive for both alkaline phosphatase and surface specific embryonic antigen-1 (SSEA-1) at a comparable level to those of mouse embryonic stem cells (ESCs). Global gene expression analysis with a 38K gene MEEBO microarray revealed that the induced colonies expressed 122 genes that are ESC-enriched, including down-regulated somatic markers and up-regulated stem cell markers. In conclusion, combined chemical treatments herein transdifferentiated or de-differentiated MEF to an intermediate state within the mesodermal lineages.
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عنوان ژورنال
دوره 6 شماره 2
صفحات -
تاریخ انتشار 2012-09-01
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