一种制备听觉细胞的简单方法

2020/8/25 16:09:41 本站原创 佚名 【字体:

廖联明    编译

 

科学家们成功地将三种不同类型的小鼠细胞重编程为毛细胞。前两种类型是生长和成熟的结缔组织细胞,称为成纤维细胞。第三种是一种不同类型的内耳细胞,称为支持细胞。

 

为了得到重编程细胞,科学家们将成纤维细胞和支持细胞暴露在四种转录因子的混合物中,这些转录因子有助于传递DNA中编码的指令的分子。

科学家们通过测试16种在新生小鼠毛细胞中高度活跃的转录因子的不同组合,确定这种混合因子的构成。

 

结果证明这四个关键构成是转录因子Six1Atoh1Pou4f3Gfi1

 

由此产生的诱导毛细胞在结构、电生理学和遗传活性方面与天然的毛细胞相似。诱导毛细胞还具有毛细胞的其他一些显著特征,包括易受到一种已知会导致听力丧失的抗生素的影响。

 

 “毛细胞很容易受损,目前人类无法修复,”Segil说,他是干细胞生物学和再生医学系的教授,USC TinaRick Caruso耳鼻咽喉头颈外科的教授,也是该研究的作者之一。衰老、噪音、某些化疗药物和抗生素都可能导致毛细胞永久性的丧失,而毛细胞是导致全球听力丧失的主要因素。”

 

据美国南加州大学约翰·道格拉斯·法兰西阿尔茨海默症基金会干细胞生物学和再生医学副教授Ichida以及该研究的另一位通讯作者说,iHCs 至少在两个重要方面可以加速听力丧失。

 

在近期内,研究人员可以使用诱导毛细胞大量筛选可能预防或治疗听力丧失的候选药物。在未来,有可能直接对失聪个体内耳中的支持细胞进行重新编程,以恢复听力。

 

 

 

A simpler way to make sensory hearing cells

 

 

The scientists successfully reprogrammed three different types of mouse cells to become iHCs. The first two types were embryonic and adult versions of connective tissue cells, known as fibroblasts. The third was a different type of inner ear cell, known as a supporting cell.

 

To achieve reprogramming, the scientists exposed fibroblasts and supporting cells to a cocktail of four transcription factors, which are molecules that help convey the instructions encoded in DNA.

 

The scientists identified this cocktail by testing various combinations of 16 transcription factors that were highly active in the hair cells of newborn mice.

 

The four key ingredients turned out to be the transcription factors Six1, Atoh1, Pou4f3, and Gfi1.

 

The resulting iHCs resembled naturally occurring hair cells in terms of their structure, electrophysiology, and genetic activity. The iHCs also possessed several other distinct characteristics of hair cells, including vulnerability to an antibiotic known to cause hearing loss.

 

"Hair cells are easy to damage, and currently impossible to repair in humans," said Segil, a professor in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology -- Head and Neck Surgery, and one of the corresponding authors of the study. "Aging, loud noises, and certain chemotherapy drugs and antibiotics can all lead to the permanent loss of hair cells, which is the leading contributor to hearing loss worldwide."

iHCs have the potential to accelerate hearing loss research in at least two important ways, according to Ichida, who is the John Douglas French Alzheimer's Foundation Associate Professor of Stem Cell Biology and Regenerative Medicine at USC, and the other corresponding author of the study.

 

In the near term, researchers can use iHCs to screen large numbers of drug candidates that might prevent or treat hearing loss. And further in the future, it could become possible to directly reprogram supporting cells in the inner ear of a deafened individual, as a way to restore hearing.

 

Journal Reference:

Generation of inner ear hair cells by direct lineage conversion of primary somatic cells. eLife, 2020; 9 DOI: 10.7554/eLife.55249

 

 

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