Transcription factor induced conversion of human fibroblasts towards the hair cell lineage
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- dc.contributor.author Duran Alonso, María Beatrizca
- dc.contributor.author López Hernández, Irisca
- dc.contributor.author Fuente, Miguel Angel de laca
- dc.contributor.author Garcia-Sancho, Javierca
- dc.contributor.author Giráldez, Fernandoca
- dc.contributor.author Schimmang, Thomasca
- dc.date.accessioned 2018-09-27T07:17:21Z
- dc.date.available 2018-09-27T07:17:21Z
- dc.date.issued 2018
- dc.description.abstract Hearing loss is the most common sensorineural disorder, affecting over 5% of the population worldwide. Its most frequent cause is the loss of hair cells (HCs), the mechanosensory receptors of the cochlea. HCs transduce incoming sounds into electrical signals that activate auditory neurons, which in turn send this information to the brain. Although some spontaneous HC regeneration has been observed in neonatal mammals, the very small pool of putative progenitor cells that have been identified in the adult mammalian cochlea is not able to replace the damaged HCs, making any hearing impairment permanent. To date, guided differentiation of human cells to HC-like cells has only been achieved using either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). However, use of such cell types suffers from a number of important disadvantages, such as the risk of tumourigenicity if transplanted into the host´s tissue. We have obtained cells expressing hair cell markers from cultures of human fibroblasts by overexpression of GFI1, Pou4f3 and ATOH1 (GPA), three genes that are known to play a critical role in the development of HCs. Immunocytochemical, qPCR and RNAseq analyses demonstrate the expression of genes typically expressed by HCs in the transdifferentiated cells. Our protocol represents a much faster approach than the methods applied to ESCs and iPSCs and validates the combination of GPA as a set of genes whose activation leads to the direct conversion of human somatic cells towards the hair cell lineage. Our observations are expected to contribute to the development of future therapies aimed at the regeneration of the auditory organ and the restoration of hearing.
- dc.description.sponsorship The project was funded by Junta de Castilla y León (Project VA024U16, Feder 2014-2020), Fundación La Marató (Project 201227-30- 31), Red de Terapia Celular and Red de medicina regenerativa y terapia celular de Castilla y León
- dc.format.mimetype application/pdf
- dc.identifier.citation Duran Alonso MB, Lopez Hernandez I, de la Fuente MA, Garcia-Sancho J, Giraldez F, Schimmang T. Transcription factor induced conversion of human fibroblasts towards the hair cell lineage. PLoS One. 2018 Jul 6;13(7):e0200210. DOI: 10.1371/journal.pone.0200210
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0200210
- dc.identifier.issn 1932-6203
- dc.identifier.uri http://hdl.handle.net/10230/35511
- dc.language.iso eng
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS One. 2018 Jul 6;13(7):e0200210
- dc.rights © 2018 Duran Alonso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Fibroblasts
- dc.subject.other Cèl·lules acústiques
- dc.title Transcription factor induced conversion of human fibroblasts towards the hair cell lineageca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion