Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea.
Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea.
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DOI：
10.1016/j.celrep.2020.108646
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发表时间：
2021-01-19
期刊：
影响因子：
8.8
通讯作者：
Heller S
中科院分区：
文献类型：
--
作者：
Kubota M;Scheibinger M;Jan TA;Heller S
在哺乳动物中，由于非感觉耳蜗细胞缺乏再生潜力，听力损失是不可逆的。然而，新生耳蜗细胞可以生长成含有感觉上皮细胞的类器官，包括毛细胞和支持细胞。在这里，我们从新生小鼠中纯化了不同的耳蜗细胞类型，用单细胞RNA测序（RNA-seq）验证了不同组的组成，并评估了各组生长成内耳类器官的潜力。我们发现，大上皮嵴（格尔），一个短暂的细胞群，出生后耳蜗成熟过程中消失，窝藏最有力的类器官形成细胞。我们确定了三个不同的格尔细胞群与一个特定的空间分布的标记基因。当细胞以增加的密度培养时，类器官形成协同增强。这种效应不是由于可扩散的信号，而是需要细胞与细胞的直接接触。我们的研究结果提高了基于细胞的检测方法的发展，以研究培养产生的内耳细胞类型。Kubota等人比较了耳蜗细胞类型的类器官形成潜力，并表明邻近新生儿Corti器官的较大上皮嵴细胞具有最强的潜力。单细胞转录组学分析证实了所有耳蜗细胞群的身份。他们的发现推进了用于开发内耳疗法的基于细胞的测定。
In mammals, hearing loss is irreversible due to the lack of regenerative potential of non-sensory cochlear cells. Neonatal cochlear cells, however, can grow into organoids that harbor sensory epithelial cells, including hair cells and supporting cells. Here, we purify different cochlear cell types from neonatal mice, validate the composition of the different groups with single-cell RNA sequencing (RNA-seq), and assess the various groups’ potential to grow into inner ear organoids. We find that the greater epithelial ridge (GER), a transient cell population that disappears during post-natal cochlear maturation, harbors the most potent organoid-forming cells. We identified three distinct GER cell groups that correlate with a specific spatial distribution of marker genes. Organoid formation was synergistically enhanced when the cells were cultured at increasing density. This effect is not due to diffusible signals but requires direct cell-to-cell contact. Our findings improve the development of cell-based assays to study culture-generated inner ear cell types. Kubota et al. compare the organoid-formation potential of cochlear cell types and show that greater epithelial ridge cells, adjacent to the neonatal organ of Corti, have the strongest potential. Single-cell transcriptomic analysis confirms the identities of all cochlear cell groups. Their findings advance cell-based assays for development of inner ear therapies.
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影响因子：
5.3
作者：
Hu, Lingxiang;Lu, Jingrong;Shi, Fuxin
通讯作者：
Shi, Fuxin
影响因子：
16.6
作者：
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通讯作者：
Bermingham-McDonogh, Olivia
DOI：
10.1073/pnas.1408064111
发表时间：
2014-11-25
影响因子：
11.1
作者：
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通讯作者：
Corfas, Gabriel
影响因子：
4.3
作者：
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