RT info:eu-repo/semantics/article
T1 Transcription factor induced conversion of human fibroblasts towards the hair cell lineage
A1 Durán Alonso, María Beatriz
A1 Fuente García, Miguel Ángel de la
A1 García-Sancho Martín, Francisco Javier
A1 Giraldez, Fernando
A1 Schimmang, Thomas
K1 Células capilares
K1 hair cell
AB 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.
PB Public Library of Science
SN 1932-6203
YR 2018
FD 2018
LK http://uvadoc.uva.es/handle/10324/32536
UL http://uvadoc.uva.es/handle/10324/32536
LA eng
NO PLoS ONE 13(7): e0200210
NO Producción Científica
DS UVaDOC
RD 28-nov-2024