Regulated Reprogramming in the Regeneration of Sensory Receptor Cells

ArticleinNeuron 71(3):389-405 · August 2011with27 Reads
DOI: 10.1016/j.neuron.2011.07.015 · Source: PubMed
Abstract
Vision, olfaction, hearing, and balance are mediated by receptors that reside in specialized sensory epithelial organs. Age-related degeneration of the photoreceptors in the retina and the hair cells in the cochlea, caused by macular degeneration and sensorineural hearing loss, respectively, affect a growing number of individuals. Although sensory receptor cells in the mammalian retina and inner ear show only limited or no regeneration, in many nonmammalian vertebrates, these sensory epithelia show remarkable regenerative potential. We summarize the current state of knowledge of regeneration in the specialized sense organs in both nonmammalian vertebrates and mammals and discuss possible areas where new advances in regenerative medicine might provide approaches to successfully stimulate sensory receptor cell regeneration. The field of regenerative medicine is still in its infancy, but new approaches using stem cells and reprogramming suggest ways in which the potential for regeneration may be restored in individuals suffering from sensory loss.
    • "The inner ear contains sensory epithelia that have a role in detecting impulses from head movements, gravity, and sound. Currently investigations are underway on how to develop these sensory epithelia from pluripotent stem cells, a process that will be critical for modeling inner ear disorders or developing cell-based therapies for underlining hearing loss and balance disorders (Brigande and Heller, 2009; Bermingham-McDonogh and Reh, 2011). The restoration of auditory function is an important subject of iPS cell studies and hearing loss is one of the most common disabilities, affecting approximately 10% of the population at different levels. "
    [Show description] [Hide description] DESCRIPTION: Throughout its half a century of development, stem cell research has included two main nd the reprogramming of body somatic cells. In the present review we focused on stem cel ryngology. The human body somatic cells are transformed into pluripotent cells by three ba ethod, the somatic cell fusion method (getting cellular pluripotent capacity in cellular repro fluencing the body somatic cells to generate reprogrammed induced pluripotent stem (i potency and differentiate into cells originating from the three germ layers; they are prefe ent, and disease modeling research. Because of ethical restrictions in obtaining ES cells, iPS and patient-specific autologous pluripotent cells are obtained by this method. Cellular trea potent cells are currently developing and we aimed to raise awareness about this topic in our ogical treatment of hearing loss, which is an important area of research in otolaryngology.
    Full-text · Research Proposal · Jan 2016 · Stem cells and development
    • "Taken together, we hypothesize that appropriate Pax6 expression in HBCs is required for the cells to differentiate into neuronal lineage cells by suppressing Sox2 expression during OE re- generation. In recent decades, regeneration in sensory organs such as the eyes, ears, and nose has received considerable attention, and the reprogramming process used in the regeneration of sensory receptor cells appears to be similar among these organs [50]. A recent study found that Pax6 + /Sox2 + / Nestin + multipotent retinal stem cells (RSCs) in the adult mouse retina are capable of producing functional photoreceptor cells [51]. "
    [Show abstract] [Hide abstract] ABSTRACT: In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal’s lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6 and are considered relatively quiescent tissue stem cells in the OE. Pax6 is a key regulator of several developmental processes in the central nervous system and in sensory organs. Although Pax6 is expressed in the OE, its precise role remains unknown, particularly with respect to stem celllike HBCs. To investigate the function of Pax6 in the developmental and regenerative processes in the OE, we generated conditional Pax6-knockout mice carrying a loxP-floxed Pax6 gene. Homozygous Pax6-floxed mice were crossed with K5-Cre transgenic mice to generate HBC-specific Pax6-knockout (Pax6-cKO) mice. We confirmed that the deletion of Pax6 expression in HBCs was sufficiently achieved in zone 1 of the OE in Pax6-cKO mice 3 days after methimazole-induced severe damage. In this condition, regeneration of the OE was dramatically impaired; both OE thickness and the number of ORNs were significantly decreased in the regenerated OE of Pax6-cKO mice. These results suggest that Pax6 expression is essential for HBCs to differentiate into neuronal cells during the regeneration process following severe injury.
    Full-text · Article · Aug 2015
    • "In recent decades, regeneration in sensory organs such as the eyes, ears, and nose has received considerable attention, and the reprogramming process used in the regeneration of sensory receptor cells appears to be similar among these organs [50]. A recent study found that Pax6+/Sox2+/Nestin+ multipotent retinal stem cells (RSCs) in the adult mouse retina are capable of producing functional photoreceptor cells [51] . "
    [Show abstract] [Hide abstract] ABSTRACT: In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal's lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6, and are considered relatively quiescent tissue stem cells in the OE. Pax6 is a key regulator of several developmental processes in the central nervous system and in sensory organs. Although Pax6 is expressed in the OE, its precise role remains unknown, particularly with respect to stem cell‒like HBCs. To investigate the function of Pax6 in the developmental and regenerative processes in the OE, we generated conditional Pax6-knockout mice carrying a loxP-floxed Pax6 gene. Homozygous Pax6-floxed mice were crossed with K5-Cre transgenic mice to generate HBC-specific Pax6-knockout (Pax6-cKO) mice. We confirmed that the deletion of Pax6 expression in HBCs was sufficiently achieved in zone 1 of the OE in Pax6-cKO mice 3 days after methimazole-induced severe damage. In this condition, regeneration of the OE was dramatically impaired; both OE thickness and the number of ORNs were significantly decreased in the regenerated OE of Pax6-cKO mice. These results suggest that Pax6 expression is essential for HBCs to differentiate into neuronal cells during the regeneration process following severe injury.
    Full-text · Article · Mar 2015
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