Down-regulation of Sox10 with specific small interfering RNA promotes transdifferentiation of Schwannoma cells into myofibroblasts.
Neural crest-derived cells are noted for the long lasting plasticity during lineage commitment process and the potential for transdifferentiation into other neural crest derivatives. Schwann cells in particular have been reported to transdifferentiate into melanocytes and myofibroblasts. Detailed studies of transdifferentiation at the molecular level have been hampered by difficulty in isolating sufficient quantity of primary cells or cellular materials. Here, we describe a robust in vitro system in which Schwannoma cells undergo an apparent transdifferentiation into myofibroblasts. Importantly, we induce the transdifferentiation by down-regulating a single transcription factor, Sox10, thereby identifying a key molecular event in this process. Myofibroblasts thus generated showed carbachol-stimulated contraction and calcium transients and express several established myofibroblast-specific genes. These results suggest that generating desired cell types based on "knock-down" of critical genes may be a viable strategy.
Roh
Jiwon
J
Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Sudaemun-gu, Seoul 120-750, Korea.
Cho
Eun-ah
EA
Seong
Ikjoo
I
Limb
Jin-kyung
JK
Lee
Sanghyuk
S
Han
Sung-jun
SJ
Kim
Jaesang
J
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009457:Neuroglia / Q000166:cytology; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D055757:SOXE Transcription Factors; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000199:Actins; D002217:Carbachol; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D034741:RNA, Small Interfering; D055757:SOXE Transcription Factors; D014157:Transcription Factors; C527925:Sox10 protein, rat; C498862:Acta2 protein, rat