Transcriptional profile of induced and primary neurons reveals new candidate genes for  lineage reprogramming

Marques‐Coelho, Diego; Souza, Sandro J. de; Costa, Marcos Romualdo

doi:10.19185/matters.201704000019

Cited by 1 publication

(1 citation statement)

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“…Future experiments using single-cell RNA sequencing (Macosko et al, 2015) and pseudotime analysis (Coelho et al, 2017;Trapnell et al, 2014) may contribute to elucidate the precise molecular mechanisms involved in neuronal fate specification during lineage reprogramming. Indeed, comparison of the transcriptional profile of fibroblasts lineage-reprogrammed into neurons and differentiating dorsal telencephalon neural progenitors reveals that both induced neurons and primary neurons display similar gene expression arrays (Coelho et al, 2017;Treutlein et al, 2016). We advocate that a systematic analysis of the transcriptional profile of astroglial cells isolated from different CNS regions and transfected with either Neurog2 or Ascl1 might be a powerful tool to uncover the molecular mechanisms of neuronal fate specification.…”

Section: Perspectivesmentioning

confidence: 99%

Instructing neuronal identity during CNS development and astroglial-lineage reprogramming: Roles of NEUROG2 and ASCL1

Chouchane

Costa

2019

Brain Research

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The adult mammalian brain contains an enormous variety of neuronal types, which are generally categorized in large groups, based on their neurochemical identity, hodological properties and molecular markers. This broad classification has allowed the correlation between individual neural progenitor populations and their neuronal progeny, thus contributing to probe the cellular and molecular mechanisms involved in neuronal identity determination during central nervous system (CNS) development. In this review, we discuss the contribution of the proneural genes Neurogenin2 (Neurog2) and Achaete-scute homolog 1 (Ascl1) for the specification of neuronal phenotypes in the developing neocortex, cerebellum and retina. Then, we revise recent data on astroglia cell lineage reprogramming into induced neurons using the same proneural proteins to compare the neuronal phenotypes obtained from astroglial cells originated in those CNS regions. We conclude that Ascl1 and Neurog2 have different contributions to determine neuronal fates, depending on the neural progenitor or astroglial population expressing those proneural factors. Finally, we discuss some possible explanations for these seemingly conflicting effects of Ascl1 and Neurog2 and propose future approaches to further dissect the molecular mechanisms of neuronal identity specification.

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