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Reprogramming of fibroblasts to a neural fate

Author: Thomas Scott VierbuchenMarius WernigPhilip Arden BeachyHoward ChangJoanna Wysocka, Ph. D.All authors
Publisher: 2012.
Dissertation: Ph. D. Stanford University 2012
Edition/Format:   Thesis/dissertation : Document : Thesis/dissertation : eBook   Computer File : English
Summary:
Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. However, recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an  Read more...
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Details

Genre/Form: Academic theses
Material Type: Document, Thesis/dissertation, Internet resource
Document Type: Internet Resource, Computer File
All Authors / Contributors: Thomas Scott Vierbuchen; Marius Wernig; Philip Arden Beachy; Howard Chang; Joanna Wysocka, Ph. D.; Stanford University. Cancer Biology Program.
OCLC Number: 809264382
Notes: Submitted to the Program in Cancer Biology.
Description: 1 online resource
Responsibility: Thomas Scott Vierbuchen.

Abstract:

Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. However, recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Similar methods can also convert human fibroblasts to functional iN cells, by forced expression of Ascl1, Brn2, Myt1l and NeuroD1. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.

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Primary Entity

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