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Decoding Neuronal Diversification by Multiplexed Single-cell RNA-Seq

delete2021-04-01
delete6
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OA
AI
J
Joachim Luginbühl
T
Tsukasa Kouno
R
Rei Nakano
T
Thomas E. Chater
D
Divya M. Sivaraman
M
Mami Kishima
F
Filip Roudnicky
P
Piero Carninci
C
Charles Plessy
J
Jay W. Shin *
DOI:10.1016/j.stemcr.2021.02.006delete
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Abstract

Abstract

En 中文
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.
Keywords:
HUMAN FIBROBLASTS
DIRECT CONVERSION
DOPAMINERGIC-NEURONS
MOUSE
PAX6
GENERATION
NEUROTRANSMITTER
REGULATORS
INDUCTION
SCREEN
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Journal

Stem Cell Reports cover
Stem Cell Reports
IF:
5.1
Papers:
2.7K
Citations:
1.1W

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R
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Scholars:
2.2W
Papers: 1.9W
Citations: 24