Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells
Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells
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DOI：
10.1242/dev.087528
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发表时间：
2013-03-01
期刊：
影响因子：
4.6
通讯作者：
Cheng, Alan Gi-Lun
中科院分区：
文献类型：
--
作者：
Jan, Taha Adnan;Chai, Renjie;Cheng, Alan Gi-Lun
永久性听力损失是由于耳蜗感觉毛细胞和非感觉支持细胞的不可逆性损伤所致。在出生后的耳蜗内，感觉上皮是终末分化的，而感觉上皮下的鼓膜边缘细胞(TbCs)是增殖的。Tbcs的功能特征较差。使用Axin2(LacZ)WNT报告小鼠，我们发现在出生后的前3周，当TBCs的数量减少时，TBCs中存在短暂但强大的Wnt信号和增殖。体内谱系追踪显示，毛细胞和支持细胞的子集是出生后从表达Axin2的TBC中衍生出来的。在耳蜗外植体中，Wnt激动剂刺激TBCs的增殖，而Wnt抑制剂抑制其增殖。此外，纯化的Axin2(LacZ)细胞在培养中具有克隆性和自我更新能力，并能分化为毛细胞样细胞和支持细胞样细胞。综上所述，我们的数据表明Axin2阳性的TBCs是Wnt反应的，并且可以作为出生后耳蜗内感觉上皮细胞的前体。
Permanent hearing loss is caused by the irreversible damage of cochlear sensory hair cells and nonsensory supporting cells. In the postnatal cochlea, the sensory epithelium is terminally differentiated, whereas tympanic border cells (TBCs) beneath the sensory epithelium are proliferative. The functions of TBCs are poorly characterized. Using an Axin2(lacZ) Wnt reporter mouse, we found transient but robust Wnt signaling and proliferation in TBCs during the first 3 postnatal weeks, when the number of TBCs decreases. In vivo lineage tracing shows that a subset of hair cells and supporting cells is derived postnatally from Axin2-expressing TBCs. In cochlear explants, Wnt agonists stimulated the proliferation of TBCs, whereas Wnt inhibitors suppressed it. In addition, purified Axin2(lacZ) cells were clonogenic and self-renewing in culture in a Wnt-dependent manner, and were able to differentiate into hair cell-like and supporting cell-like cells. Taken together, our data indicate that Axin2-positive TBCs are Wnt responsive and can act as precursors to sensory epithelial cells in the postnatal cochlea.