Characterization of the development of the mouse cochlear epithelium at the single cell level

被引:184
作者
Kolla, Likhitha [1 ]
Kelly, Michael C. [1 ]
Mann, Zoe F. [2 ]
Anaya-Rocha, Alejandro [1 ]
Ellis, Kathryn [1 ]
Lemons, Abigail [1 ]
Palermo, Adam T. [3 ]
So, Kathy S. [3 ]
Mays, Joseph C. [1 ]
Orvis, Joshua [4 ]
Burns, Joseph C. [3 ]
Hertzano, Ronna [4 ,5 ]
Driver, Elizabeth C. [1 ]
Kelley, Matthew W. [1 ]
机构
[1] NIDCD, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA
[2] Kings Coll London, Ctr Craniofacial & Regenerat Biol, London, England
[3] Decibel Therapeut, 1325 Boylston Str,Suite 500, Boston, MA 02215 USA
[4] Univ Maryland, Inst Genome Sci, Sch Med, Baltimore, MD 21201 USA
[5] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg Anat & Neu, Baltimore, MD 21201 USA
关键词
FIBROBLAST-GROWTH-FACTOR; INNER-EAR; HEARING-LOSS; HAIR-CELLS; BINDING-PROTEINS; GENE-EXPRESSION; FATE DECISIONS; SENSORY ORGAN; DEAFNESS; SPECIFICATION;
D O I
10.1038/s41467-020-16113-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgf beta r1 is identified as being expressed in lateral progenitor cells and a Tgf beta r1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set. How the development of the cochlear epithelium is regulated is unclear. Here, the authors use single cell RNAseq analysis to provide insight into the transcriptional changes arising during development of the murine cochlear inner and outer hair cells.
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页数:16
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