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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 313304.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Signals from embryonic fibroblasts induce adult intestinal epithelial cells to form nestin-positive cells with proliferation and multilineage differentiation capacity in vitro
Authors:Wiese, C.; Rolletschek, A.; Kania, G.; Navarrete-Santos, A.; Anisimov, S. V.; Steinfarz, B.; Tarasov, K. V.; Brugh, S. A.; Zahanich, I.; Ruschenschmidt, C.; Beck, H.; Blyszczuk, P.; Czyz, J.; Heubach, J. F.; Ravens, U.; Horstmann, O.; St-Onge, L.; Braun, T.; Brustle, O.; Boheler, K. R.; Wobus, A. M.
Date of Publication (YYYY-MM-DD):2006-09
Title of Journal:Stem Cells
Journal Abbrev.:Stem Cells
Issue / Number:9
Start Page:2085
End Page:2097
Audience:Not Specified
Abstract / Description:The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an "artificial niche" of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin-positive cells (intestinal epithelium-derived nestin-positive cells [INPs]). Transcriptome analyses demonstrated that mouse embryonic fibroblasts expressed relatively high levels of Wnt/bone morphogenetic protein (BMP) transcripts, and the formation of INPs was specifically associated with an increase in Lef1, Wnt4, Wnt5a, and Wnt/BMP-responsive factors, but a decrease of BMP4 transcript abundance. In vitro, INPs showed a high but finite proliferative capacity and readily differentiated into cells expressing neural, pancreatic, and hepatic transcripts and proteins; however, these derivatives did not show functional properties. In vivo, INPs failed to form chimeras following injection into mouse blastocysts but integrated into hippocampal brain slice cultures in situ. We conclude that the use of embryonic fibroblasts seems to reprogram adult intestinal epithelial cells by modulation of Wnt/BMP signaling to a cell type with a more primitive embryonic-like stage of development that has a high degree of flexibility and plasticity.
Free Keywords:Animals Bone Morphogenetic Proteins/genetics *Cell Differentiation *Cell Lineage *Cell Proliferation Cells, Cultured Ectoderm/cytology Endoderm/cytology Enterocytes/*cytology Fibroblasts/*cytology Gene Expression Profiling Humans Intermediate Filament Proteins/*metabolism Mice Nerve Tissue Proteins/*metabolism Polymerase Chain Reaction RNA, Messenger/genetics/metabolism *Signal Transduction Up-Regulation/genetics Wnt Proteins/genetics
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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