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Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
Author(s) -
Ma NingXin,
Puls Brendan,
Chen Gong
Publication year - 2022
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22882
Subject(s) - biology , neurod , astrocyte , microbiology and biotechnology , transcriptome , reprogramming , oligodendrocyte , neuroscience , transcription factor , myelin , gene expression , genetics , gene , central nervous system
Abstract Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA‐sequencing technology to capture the transcriptomic changes at different time points during the reprogramming process. We found that following NeuroD1 overexpression, astroglial genes (ACTG1, ALDH1A3, EMP1, CLDN6, SOX21) were significantly downregulated, whereas neuronal genes (DCX, RBFOX3/NeuN, CUX2, RELN, SNAP25) were significantly upregulated. NeuroD family members (NeuroD1/2/6) and signaling pathways (Wnt, MAPK, cAMP) as well as neurotransmitter receptors (acetylcholine, somatostatin, dopamine) were also significantly upregulated. Gene co‐expression analysis identified many central genes among the NeuroD1‐interacting network, including CABP7, KIAA1456, SSTR2, GADD45G, LRRTM2, and INSM1. Compared to chemical conversion, we found that NeuroD1 acted as a strong driving force and triggered fast transcriptomic changes during astrocyte‐to‐neuron conversion process. Together, this study reveals many important downstream targets of NeuroD1 such as HES6, BHLHE22, INSM1, CHRNA1/3, CABP7, and SSTR2, which may play critical roles during the transcriptomic landscape shift from a glial profile to a neuronal profile.