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  • In vivo ectopic Ngn1 and Neurod1 convert neonatal cochlear glial cells into spiral ganglion neurons.

In vivo ectopic Ngn1 and Neurod1 convert neonatal cochlear glial cells into spiral ganglion neurons.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2020-02-07)
Xiang Li, Zhenghong Bi, Yidi Sun, Chao Li, Yixue Li, Zhiyong Liu
ABSTRACT

Damage or degeneration of inner ear spiral ganglion neurons (SGNs) causes hearing impairment. Previous in vitro studies indicate that cochlear glial cells can be reprogrammed into SGNs, however, it remains unknown whether this can occur in vivo. Here, we show that neonatal glial cells can be converted, in vivo, into SGNs (defined as new SGNs) by simultaneous induction of Neurog1 (Ngn1) and Neurod1. New SGNs express SGN markers, Tuj1, Map2, Prox1, Mafb and Gata3, and reduce glial cell marker Sox10 and Scn7a. The heterogeneity within new SGNs is illustrated by immunostaining and transcriptomic assays. Transcriptomes analysis indicates that well reprogrammed SGNs are similar to type I SGNs. In addition, reprogramming efficiency is positively correlated with the dosage of Ngn1 and Neurod1, but declined with aging. Taken together, our in vivo data demonstrates the plasticity of cochlear neonatal glial cells and the capacity of Ngn1 and Neurod1 to reprogram glial cells into SGNs. Looking ahead, we expect that combination of Neurog1 and Neurod1 along with other factors will further boost the percentage of fully converted (Mafb+/Gata3+) new SGNs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tamoxifen, ≥99%
Sigma-Aldrich
Corn oil, delivery vehicle for fat-soluble compounds
Sigma-Aldrich
SYBR® Green JumpStart Taq ReadyMix, for quantitative PCR, MgCI2 in buffer
Sigma-Aldrich
Anti-MAP2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Prox 1 Antibody, serum, Chemicon®
Sigma-Aldrich
Anti-MAFB antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution