Nature Biotechnology
20, 460 - 466 (2002)
doi:10.1038/nbt0502-460
Reprogramming fibroblasts to express T-cell functions using cell
extractsAnne-Mari Håkelien1, 3, Helga B. Landsverk1, James M. Robl3, Bjørn S. Skålhegg2
& Philippe Collas1, 31
Institute of Medical Biochemistry,
P.O. Box 1112, Blindern, University of Oslo,
Oslo 0317, Norwayand. 2
Institute for Nutrition Research,
P.O. Box 1046 Blindern, University of Oslo,
Oslo 0317, Norway. 3
Nucleotech LLC, 33 Riverside
Avenue, Westport, CT 06880.
Correspondence should be addressed to Philippe Collas philippe.collas@basalmed.uio.noWe demonstrate here the functional reprogramming of a somatic cell
using a nuclear and cytoplasmic extract derived from another somatic cell type.
Reprogramming of 293T fibroblasts in an extract from primary human T cells or
from a transformed T-cell line is evidenced by nuclear uptake and assembly of
transcription factors, induction of activity of a chromatin remodeling complex,
histone acetylation, and activation of lymphoid cell−specific genes.
Reprogrammed cells express T cell−specific receptors and assemble the
interleukin-2 receptor in response to T cell receptor−CD3 (TCR−CD3)
complex stimulation. Reprogrammed primary skin fibroblasts also express T
cell−specific antigens. After exposure to a neuronal precursor extract,
293T fibroblasts express a neurofilament protein and extend neurite-like
outgrowths. In vitro reprogramming of differentiated somatic cells
creates possibilities for producing isogenic replacement cells for therapeutic
applications.
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