CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons

Stem Cell Reports
Katerina Aravantinou-FatorouDimitra Thomaidou

Abstract

Recent studies demonstrate that astroglia from non-neurogenic brain regions can be reprogrammed into functional neurons through forced expression of neurogenic factors. Here we explored the effect of CEND1 and NEUROG2 on reprogramming of mouse cortical astrocytes and embryonic fibroblasts. Forced expression of CEND1, NEUROG2, or both resulted in acquisition of induced neuronal cells expressing subtype-specific markers, while long-term live-cell imaging highlighted the existence of two different modes of neuronal trans-differentiation. Of note, a subpopulation of CEND1 and NEUROG2 double-transduced astrocytes formed spheres exhibiting neural stem cell properties. mRNA and protein expression studies revealed a reciprocal feedback loop existing between the two molecules, while knockdown of endogenous CEND1 demonstrated that it is a key mediator of NEUROG2-driven neuronal reprogramming. Our data suggest that common reprogramming mechanisms exist driving the conversion of lineage-distant somatic cell types to neurons and reveal a critical role for CEND1 in NEUROG2-driven astrocytic reprogramming.

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Citations

Apr 11, 2018·Stem Cells and Development·Xiaoqing ZhuTianqing Li
Mar 27, 2019·Journal of Cellular Physiology·Masoumeh Zarei-KheirabadiHossein Baharvand
Apr 12, 2019·Frontiers in Neuroscience·Gaia ColasanteVania Broccoli
Dec 12, 2019·Neural Regeneration Research·Brian B GriffithsCreed M Stary
Sep 25, 2017·Methods : a Companion to Methods in Enzymology·Ebrahim ShahbaziHossein Baharvand
May 17, 2017·Stem Cell Reports·Rebecca BruletJenny Hsieh
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Raphaela Almeida ChiareliMauro Cunha Xavier Pinto

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Methods Mentioned

BETA
PCR

Software Mentioned

TTT
Timm
s Tracking Tool ( TTT )

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