Characterization of Hair Cell-Like Cells Converted From Supporting Cells After Notch Inhibition in Cultures of the Organ of Corti From Neonatal Gerbils.
Characterization of Hair Cell-Like Cells Converted From Supporting Cells After Notch Inhibition in Cultures of the Organ of Corti From Neonatal Gerbils.
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新生沙鼠柯蒂氏器官培养物中缺口抑制后支持细胞转化的毛细胞样细胞的表征
DOI：
10.3389/fncel.2018.00073
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发表时间：
2018
影响因子：
5.3
通讯作者：
He DZZ
中科院分区：
文献类型：
--
作者：
Li Y;Jia S;Liu H;Tateya T;Guo W;Yang S;Beisel KW;He DZZ
听觉和平衡感依赖于毛细胞，内耳的感觉受体。毛细胞将机械刺激转换为电活动。由于老化或暴露于噪音和耳毒性药物而导致的毛细胞损失是非先天性听力和平衡缺陷的主要原因。在非哺乳动物的耳中，失去的毛细胞可以自发地被来自支持细胞转化的新毛细胞的产生所取代。虽然成年哺乳动物的支持细胞已经失去了这种能力，但新生儿的支持细胞在抑制Notch信号传导后能够转化为毛细胞。我们质疑Notch抑制是否足以使用电生理学和电子显微镜将支持细胞转化为功能性毛细胞。我们发现，药理学抑制的经典Notch途径在培养的器官的Corti制备的新生沙鼠诱导静纤毛形成支持细胞（定义为毛细胞样细胞或HCLC）和多余的静纤毛毛细胞。新出现的HCLC静纤毛束是功能性的，即，能够对具有机械传导（MET）电流的机械刺激作出响应。透射电子显微镜（TEM）显示，柱细胞转化的HCLC保持柱细胞的形状和亚表面池，通常观察到的细胞骨架下的外毛细胞（OHC），不存在于Deiters细胞衍生的HCLC。电压钳记录显示，来自Deiters细胞衍生的HCLC的全细胞电流保留了在正常Deiters细胞中观察到的相同动力学和幅度，并且未从测量的任何HCLC中检测到非线性电容（NLC）（OHC电运动的电标志）。总之，这些结果表明，虽然Notch抑制足以促进静纤毛束形成，但不足以将新生支持细胞转化为成熟毛细胞。Notch抑制导致支持细胞中的静纤毛形成和现有毛细胞中的多余静纤毛的事实似乎表明Notch信号传导可以调节发育期间的静纤毛形成和稳定性。
The senses of hearing and balance depend upon hair cells, the sensory receptors of the inner ear. Hair cells transduce mechanical stimuli into electrical activity. Loss of hair cells as a result of aging or exposure to noise and ototoxic drugs is the major cause of noncongenital hearing and balance deficits. In the ear of non-mammals, lost hair cells can spontaneously be replaced by production of new hair cells from conversion of supporting cells. Although supporting cells in adult mammals have lost that capability, neonatal supporting cells are able to convert to hair cells after inhibition of Notch signaling. We questioned whether Notch inhibition is sufficient to convert supporting cells to functional hair cells using electrophysiology and electron microscopy. We showed that pharmacological inhibition of the canonical Notch pathway in the cultured organ of Corti prepared from neonatal gerbils induced stereocilia formation in supporting cells (defined as hair cell-like cells or HCLCs) and supernumerary stereocilia in hair cells. The newly emerged stereocilia bundles of HCLCs were functional, i.e., able to respond to mechanical stimulation with mechanotransduction (MET) current. Transmission electron microscopy (TEM) showed that HCLCs converted from pillar cells maintained the pillar cell shape and that subsurface cisternae, normally observed underneath the cytoskeleton in outer hair cells (OHCs), was not present in Deiters’ cells-derived HCLCs. Voltage-clamp recordings showed that whole-cell currents from Deiters’ cells-derived HCLCs retained the same kinetics and magnitude seen in normal Deiters’ cells and that nonlinear capacitance (NLC), an electrical hallmark of OHC electromotility, was not detected from any HCLCs measured. Taken together, these results suggest that while Notch inhibition is sufficient for promoting stereocilia bundle formation, it is insufficient to convert neonatal supporting cells to mature hair cells. The fact that Notch inhibition led to stereocilia formation in supporting cells and supernumerary stereocilia in existing hair cells appears to suggest that Notch signaling may regulate stereocilia formation and stability during development.
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DOI：
10.1002/neu.10002
发表时间：
2002-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Gale, JE;Meyers, JR;Corwin, JT
通讯作者：
Corwin, JT
DOI：
10.1016/s0165-3806(97)00120-x
发表时间：
1997-10-20
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
He, DZZ;Dallos, P
通讯作者：
Dallos, P
影响因子：
4.5
作者：
Kiernan AE;Xu J;Gridley T
通讯作者：
Gridley T
影响因子：
64.8
作者：
Gubbels, Samuel P.;Woessner, David W.;Mitchell, John C.;Ricci, Anthony J.;Brigande, John V.
通讯作者：
Brigande, John V.
影响因子：
7.7
作者：
Basch ML;Brown RM 2nd;Jen HI;Semerci F;Depreux F;Edlund RK;Zhang H;Norton CR;Gridley T;Cole SE;Doetzlhofer A;Maletic-Savatic M;Segil N;Groves AK
通讯作者：
Groves AK