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Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes.

Abstract：

:We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types of mature cortical projection neurons defined by their distinct gene-expression profiles. Moreover, exactly how and when neurons diversify their function during development is unknown. Here we relate gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversify neuron cell fate. We compare these gene-expression profiles with published profiles of single cells isolated from similar populations and establish that layer-defined cell classes encompass cell subtypes and developmental trajectories identified using single-cell sequencing. Given the depth of our sequencing, we identify groups of transcription factors with particularly dense subclass-specific regulation and subclass-enriched transcription factor binding motifs. We also describe transcription factor-adjacent long noncoding RNAs that define each subclass and validate the function of Myt1l in balancing the ratio of the two subclasses in vitro. Our multidimensional approach supports an evolving model of progressive restriction of cell fate competence through inherited transcriptional identities.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Heavner WE,Ji S,Notwell JH,Dyer ES,Tseng AM,Birgmeier J,Yoo B,Bejerano G,McConnell SK

doi

10.1073/pnas.2008013117

subject

Has Abstract

pub_date

2020-10-06 00:00:00

pages

25074-25084

issue

eissn

0027-8424

issn

1091-6490

pii

2008013117

journal_volume

117

pub_type

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Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes.