Decoding Neuronal Diversification by Multiplexed Single-cell RNA-Seq

被引:6
作者
Luginbuhl, Joachim [1 ,2 ]
Kouno, Tsukasa [1 ,2 ]
Nakano, Rei [1 ,3 ]
Chater, Thomas E. [4 ]
Sivaraman, Divya M. [1 ,2 ,5 ]
Kishima, Mami [1 ,2 ]
Roudnicky, Filip [6 ]
Carninci, Piero [1 ,2 ]
Plessy, Charles [1 ,2 ]
Shin, Jay W. [1 ,2 ]
机构
[1] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan
[2] RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa 2300045, Japan
[3] Nihon Univ, Coll Bioresource Sci, Lab Vet Radiol, Fujisawa, Kanagawa 2520880, Japan
[4] RIKEN Ctr Brain Sci, Wako, Saitama 3510198, Japan
[5] Sree Chitra Tirunal Inst Med Sci & Technol, Dept Pathol, Thiruvananthapuram 695011, Kerala, India
[6] Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8057 Zurich, Switzerland
来源
STEM CELL REPORTS | 2021年 / 16卷 / 04期
基金
日本学术振兴会;
关键词
HUMAN FIBROBLASTS; DIRECT CONVERSION; DOPAMINERGIC-NEURONS; MOUSE; PAX6; GENERATION; NEUROTRANSMITTER; REGULATORS; INDUCTION; SCREEN;
D O I
10.1016/j.stemcr.2021.02.006
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Cellular reprogramming is driven by a defined set of transcription factors; however, the regulatory logic that underlies cell-type specifi-cation and diversification remains elusive. Single-cell RNA-seq provides unprecedented coverage to measure dynamic molecular changes at the single-cell resolution. Here, we multiplex and ectopically express 20 pro-neuronal transcription factors in human dermal fibroblasts and demonstrate a widespread diversification of neurons based on cell morphology and canonical neuronal marker expressions. Single-cell RNA-seq analysis reveals diverse and distinct neuronal subtypes, including reprogramming processes that strongly correlate with the developing brain. Gene mapping of 20 exogenous pro-neuronal transcription factors further unveiled key determinants responsible for neuronal lineage specification and a regulatory logic dictating neuronal diversification, including glutamatergic and cholinergic neurons. The multiplex scRNA-seq approach is a robust and scalable approach to elucidate lineage and cellular specification across various biolog-ical systems.
引用
收藏
页码:810 / 824
页数:15
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