scholarly journals Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle

Aging ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 19834-19851
Author(s):  
Yuan Zhang ◽  
Shasha Zhang ◽  
Zhonghong Zhang ◽  
Ying Dong ◽  
Xiangyu Ma ◽  
...  
Keyword(s):  
Hair Cells ◽  
Neonatal Mouse ◽  
Supporting Cells

scholarly journals Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea

2019 ◽  
Vol 77 (7) ◽  
pp. 1401-1419 ◽  
Author(s):  
Shasha Zhang ◽  
Yuan Zhang ◽  
Ying Dong ◽  
Lingna Guo ◽  
Zhong Zhang ◽  
...  
Keyword(s):  
Hair Cells ◽  
Neonatal Mouse ◽  
Supporting Cells

Electron Microscopic Findings in Presbycusic Degeneration of the Basal Turn of the Human Cochlea

1979 ◽  
Vol 87 (6) ◽  
pp. 818-836 ◽  
Author(s):  
Joseph B. Nadol
Keyword(s):  
Light Microscopy ◽  
Hair Cells ◽  
Basilar Membrane ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Degenerative Changes ◽  
Supporting Cells ◽  
Neural Degeneration ◽  
Basal Turn ◽  
Temporal Bones

Three human temporal bones with presbycusis affecting the basal turn of the cochlea were studied by light and electron microscopy. Conditions in two ears examined by light microscopy were typical of primary neural degeneration, with a descending audiometric pattern, loss of cochlear neurons in the basal turn, and preservation of the organ of Corti. Ultrastructural analysis revealed normal hair cells and marked degenerative changes of the remaining neural fibers, especially in the basal turn. These changes included a decrease in the number of synapses at the base of hair cells, accumulation of cellular debris in the spiral bundles, abnormalities of the dendritic fibers and their sheaths in the osseous spiral lamina, and degenerative changes in the spiral ganglion cells and axons. These changes were interpreted as an intermediate stage of degeneration prior to total loss of nerve fibers and ganglion cells as visualized by light microscopy. In the third ear the changes observed were typical of primary degeneration of hair and supporting cells in the basal turn with secondary neural degeneration. Additional observations at an ultrastructural level included maintenance of the tight junctions of the scala media despite loss of both hair and supporting cells, suggesting a capacity for cellular “healing” in the inner ear. Degenerative changes were found in the remaining neural fibers in the osseous spiral lamina. In addition, there was marked thickening of the basilar membrane in the basal turn, which consisted of an increased number of fibrils and an accumulation of amorphous osmiophilic material in the basilar membrane. This finding supports the concept that mechanical alterations may occur in presbycusis of the basal turn.

Electrophysiological Properties of Vestibular Sensory and Supporting Cells in the Labyrinth Slice Before and During Regeneration

1997 ◽  
Vol 78 (4) ◽  
pp. 1913-1927 ◽  
Author(s):  
Sergio Masetto ◽  
Manning J. Correia
Keyword(s):  
Hair Cells ◽  
Semicircular Canal ◽  
Ionic Currents ◽  
Ionic Channels ◽  
Membrane Properties ◽  
Supporting Cells ◽  
Mean Values ◽  
Electrophysiological Properties ◽  
Current Voltage ◽  
Zone Ii

Masetto, Sergio and Manning J. Correia. Electrophysiological properties of vestibular sensory and supporting cells in the labyrinth slice before and during regeneration. J. Neurophysiol. 78: 1913–1927, 1997. The whole cell patch-clamp technique in combination with the slice preparation was used to investigate the electrophysiological properties of pigeon semicircular canal sensory and supporting cells. These properties were also characterized in regenerating neuroepithelia of pigeons preinjected with streptomycin to kill the hair cells. Type II hair cells from each of the three semicircular canals showed similar, topographically related patterns of passive and active membrane properties. Hair cells located in the peripheral regions (zone I, near the planum semilunatum) had less negative resting potentials [0-current voltage in current-clamp mode ( V z) = −62.8 ± 8.7 mV, mean ± SD; n = 13] and smaller membrane capacitances ( C m = 5.0 ± 0.9 pF, n = 14) than cells of the intermediate (zone II; V z = −79.3 ± 7.5 mV, n = 3; C m = 5.9 ± 1.2 pF, n = 4) and central (zone III; V z = −68.0 ± 9.6 mV, n = 17; C m = 7.1 ± 1.5 pF, n = 18) regions. In peripheral hair cells, ionic currents were dominated by a rapidly activating/inactivating outward K+ current, presumably an A-type K+ current ( I KA). Little or no inwardly rectifying current was present in these cells. Conversely, ionic currents of central hair cells were dominated by a slowly activating/inactivating outward K+ current resembling a delayed rectifier K+ current ( I KD). Moreover, an inward rectifying current at voltages negative to −80 mV was present in all central cells. This current was composed of two components: a slowly activating, noninactivating component ( I h), described in photoreceptors and saccular hair cells, and a faster-activating, partially inactivating component ( I K1) also described in saccular hair cells in some species. I h and I K1 were sometimes independently expressed by hair cells. Hair cells located in the intermediate region (zone II) had ionic currents more similar to those of central hair cells than peripheral hair cells. Outward currents in intermediate hair cells activated only slightly more quickly than those of the cells of the central region, but much more slowly than those of the peripheral cells. Additionally, intermediate hair cells, like central hair cells, always expressed an inward rectifying current. The regional distribution of outward rectifying potassium conductances resulted in macroscopic currents differing in peak–to–steady state ratio. We quantified this by measuring the peak ( G p) and steady-state ( G s) slope conductance in the linear region of the current-voltage relationship (−40 to 0 mV) for the hair cells located in the different zones. G p/ G s average values (4.1 ± 2.1, n = 15) from currents in peripheral hair cells were higher than those from intermediate hair cells (2.3 ± 0.8, n = 4) and central hair cells(1.9 ± 0.8, n = 21). The statistically significant differences ( P < 0.001) in G p/ G s ratios could be accounted for by KA channels being preferentially expressed in peripheral hair cells. Hair cell electrophysiological properties in animals pretreated with streptomycin were investigated at ∼3 wk and ∼9–10 wk post injection sequence (PIS). At 3 wk PIS, hair cells (all zones combined) had a statistically significantly ( P < 0.001) lower C m (4.6 ± 1.1 pF, n = 24) and a statistically significantly ( P < 0.01) lower G p(48.4 ± 20.8 nS, n = 26) than control animals ( C m = 6.2 ± 1.6 pF, n = 36; G p = 66 ± 38.9 nS, n = 40). Regional differences in values of V z, as well as the distribution of outward and inward rectifying currents, seen in control animals, were still obvious. But, differences in the relative contribution of the expression of the different ionic current components changed. This result could be explained by a relative decrease in I KA compared with I KD during that interval of regeneration, which was particularly evident in peripheral hair cells. At 9–10 wk PIS, hair cells of all zones had membrane properties not statistically different ( P > 0.5) from those in untreated normal animals. C m was 6.1 ± 1.3 pF ( n = 30) and G p was 75.9 ± 36.6 nS ( n = 30). Thus it appears that during regeneration, avian semicircular canal type II hair cells are likely to recover all their functional properties. At 9–10 wk PIS, regenerated hair cells expressed the same macroscopic ionic currents and had the same topographic distribution as normal hair cells. Measurements obtained at 3 wk PIS suggest that regenerated hair cells come from smaller cells (smaller mean values of C m) endowed with fewer potassium channels (smaller mean values of G p). In addition, differences observed in peripheral hair cells' kinetics and G p/ G s ratios at 3 wk PIS suggest that different ionic channels follow different schedules of expression during hair cell regeneration. We recorded from nine supporting cells both in normal ( n = 5) and regenerating ( n = 4) epithelia. These cells had an average negative resting potential of V z = −49.5 ± 14.1 mV ( n = 9), but no obvious sign of voltage- and time-dependent ionic currents, except for a very weak inward rectification at very negative potentials, both in normal and streptomycin-recovering animals. Therefore, if all semicircular canal supporting cells are like the small sample we tested and if supporting cells are actually the progenitors of regenerating hair cells, then they must change shape, develop hair bundles, become reinnervated, and also acquire a complete set of ionic channels ex novo.

Cis-Diamminedichloroplatinum (II) Ototoxicity in the Guinea Pig

1981 ◽  
Vol 89 (4) ◽  
pp. 638-645 ◽  
Author(s):  
Scott A. Estrem ◽  
Richard W. Babin ◽  
Jai H. Ryu ◽  
Kenneth C. Moore
Keyword(s):  
Electron Microscopy ◽  
Hair Cells ◽  
Supporting Cell ◽  
Cell Ultrastructure ◽  
Outer Hair Cells ◽  
Detectable Change ◽  
Supporting Cells ◽  
Apical Portion ◽  
Ultrastructural Evidence ◽  
Transmission Electron

Cochleas from 12 guinea pigs were evaluated using light, scanning, and transmission electron microscopy after systemic administration of cis-diamminedichloroplatinum (cis-DDP). Administration of cis-DDP resulted in loss of the Preyer reflex and degeneration of outer hair cells (OHC) with increased dose. The OHC degeneration was most pronounced in the basal turns of the cochlea with greatest severity in the inner row. Ultrastructural evidence of OHC degeneration included dilatation of the parietal membranes, softening of the cuticular plate, increased vacuolization and increased numbers of lysosome-like bodies in the apical portion of the cell. Supporting cells appeared more sensitive than OHC. Alteration of supporting cell ultrastructure preceded detectable change in OHC. Injury to the supporting cells was noted with intracellular vesiculation and increased autophagocytosis.

p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1581-1590 ◽  
Author(s):  
P. Chen ◽  
N. Segil
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Inner Ear ◽  
Hair Cells ◽  
Cellular Proliferation ◽  
Adult Life ◽  
Organ Of Corti ◽  
Morphological Development ◽  
Supporting Cells ◽  
P27 Kip1

Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed precisely along the length of the spiral cochlea. In mice, the progenitors of greater than 80% of both hair cells and supporting cells undergo their terminal division between embryonic day 13 (E13) and E14. As in humans, these cells persist in a non-proliferative state throughout the adult life of the animal. Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. Homozygous mutant mice are severely hearing impaired. Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear.

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4637-4644 ◽  
Author(s):  
C. Haddon ◽  
Y.J. Jiang ◽  
L. Smithers ◽  
J. Lewis
Keyword(s):  
Cell Differentiation ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Types ◽  
Notch Signalling ◽  
Supporting Cells ◽  
Fine Grained ◽  
Mechanosensory Hair Cells ◽  
The Mind

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

scholarly journals Generation of Cochlear Hair Cells from Sox2 Positive Supporting Cells via DNA Demethylation

2020 ◽  
Vol 21 (22) ◽  
pp. 8649
Author(s):  
Xin Deng ◽  
Zhengqing Hu
Keyword(s):  
Transgenic Mice ◽  
Inner Ear ◽  
Hair Cells ◽  
Dna Methyltransferase ◽  
Dna Demethylation ◽  
Egfp Expression ◽  
Supporting Cells ◽  
Cochlear Hair Cells ◽  
Auditory Hair Cells ◽  
Adult Mice

Regeneration of auditory hair cells in adult mammals is challenging. It is also difficult to track the sources of regenerated hair cells, especially in vivo. Previous paper found newly generated hair cells in deafened mouse by injecting a DNA methyltransferase inhibitor 5-azacytidine into the inner ear. This paper aims to investigate the cell sources of new hair cells. Transgenic mice with enhanced green fluorescent protein (EGFP) expression controlled by the Sox2 gene were used in the study. A combination of kanamycin and furosemide was applied to deafen adult mice, which received 4 mM 5-azacytidine injection into the inner ear three days later. Mice were followed for 3, 5, 7 and 14 days after surgery to track hair cell regeneration. Immunostaining of Myosin VIIa and EGFP signals were used to track the fate of Sox2-expressing supporting cells. The results show that (i) expression of EGFP in the transgenic mice colocalized the supporting cells in the organ of Corti, and (ii) the cell source of regenerated hair cells following 5-azacytidine treatment may be supporting cells during 5–7 days post 5-azacytidine injection. In conclusion, 5-azacytidine may promote the conversion of supporting cells to hair cells in chemically deafened adult mice.

scholarly journals LIN28B/let-7control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling

2020 ◽  
Vol 117 (36) ◽  
pp. 22225-22236
Author(s):  
Xiao-Jun Li ◽  
Angelika Doetzlhofer
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Rna Binding ◽  
Mammalian Target Of Rapamycin ◽  
Cell Loss ◽  
Supporting Cell ◽  
Dependent Manner ◽  
Cell Plasticity ◽  
Supporting Cells ◽  
Cochlear Hair Cells

Mechano-sensory hair cells within the inner ear cochlea are essential for the detection of sound. In mammals, cochlear hair cells are only produced during development and their loss, due to disease or trauma, is a leading cause of deafness. In the immature cochlea, prior to the onset of hearing, hair cell loss stimulates neighboring supporting cells to act as hair cell progenitors and produce new hair cells. However, for reasons unknown, such regenerative capacity (plasticity) is lost once supporting cells undergo maturation. Here, we demonstrate that the RNA binding protein LIN28B plays an important role in the production of hair cells by supporting cells and provide evidence that the developmental drop in supporting cell plasticity in the mammalian cochlea is, at least in part, a product of declining LIN28B-mammalian target of rapamycin (mTOR) activity. Employing murine cochlear organoid and explant cultures to model mitotic and nonmitotic mechanisms of hair cell generation, we show that loss of LIN28B function, due to its conditional deletion, or due to overexpression of the antagonistic miRNAlet-7g, suppressed Akt-mTOR complex 1 (mTORC1) activity and renders young, immature supporting cells incapable of generating hair cells. Conversely, we found that LIN28B overexpression increased Akt-mTORC1 activity and allowed supporting cells that were undergoing maturation to de-differentiate into progenitor-like cells and to produce hair cells via mitotic and nonmitotic mechanisms. Finally, using the mTORC1 inhibitor rapamycin, we demonstrate that LIN28B promotes supporting cell plasticity in an mTORC1-dependent manner.

Sign in / Sign up

Export Citation Format

Share Document