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Generation of sensory hair cells by genetic programming with a combination of transcription factors

Costa, A; Sanchez-Guardado, L; Juniat, S; Gale, JE; Daudet, N; Henrique, D; (2015) Generation of sensory hair cells by genetic programming with a combination of transcription factors. Development , 142 (11) pp. 1948-1959. 10.1242/dev.119149. Green open access

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Abstract

Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.

Type: Article
Title: Generation of sensory hair cells by genetic programming with a combination of transcription factors
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.119149
Publisher version: http://dx.doi.org/10.1242/dev.119149
Language: English
Additional information: © 2015. Published by The Company of Biologists Ltd
Keywords: Atoh1, Cell type programming, Gene regulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1469789
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