Transcriptional heterogeneity of ventricular zone cells in the ganglionic eminences of the mouse forebrain

  1. Dongjin R Lee
  2. Christopher Rhodes
  3. Apratim Mitra
  4. Yajun Zhang
  5. Dragan Maric
  6. Ryan K Dale
  7. Timothy J Petros  Is a corresponding author
  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States
  2. National Institute of Neurological Disease and Stroke, United States

Abstract

The ventricular zone (VZ) of the nervous system contains radial glia cells that were originally considered relatively homogenous in their gene expression, but a detailed characterization of transcriptional diversity in these VZ cells has not been reported. Here, we performed single-cell RNA sequencing to characterize transcriptional heterogeneity of neural progenitors within the VZ and subventricular zone (SVZ) of the ganglionic eminences (GEs), the source of all forebrain GABAergic neurons. By using a transgenic mouse line to enrich for VZ cells, we characterize significant transcriptional heterogeneity, both between GEs and within spatial subdomains of specific GEs. Additionally, we observe differential gene expression between E12.5 and E14.5 VZ cells, which could provide insights into temporal changes in cell fate. Together, our results reveal a previously unknown spatial and temporal genetic diversity of VZ cells in the ventral forebrain that will aid our understanding of initial fate decisions in the forebrain.

Data availability

All of our sequencing data has been deposited in GEO under accession code GSE167013 and GSE190593.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Dongjin R Lee

    Unit on Cellular and Molecular Neurodevelopment, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher Rhodes

    Unit on Cellular and Molecular Neurodevelopment, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7438-4236
  3. Apratim Mitra

    Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yajun Zhang

    Unit on Cellular and Molecular Neurodevelopment, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dragan Maric

    Flow and Imaging Cytometry Core, National Institute of Neurological Disease and Stroke, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ryan K Dale

    Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Timothy J Petros

    Unit on Cellular and Molecular Neurodevelopment, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    For correspondence
    tim.petros@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8943-546X

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intramural Award)

  • Timothy J Petros

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Carol A Mason, Columbia University, United States

Ethics

Animal experimentation: All mouse colonies were maintained in accordance with protocols approved by the Animal Care and Use Committee at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under animal study protocol ASP #20-047.

Version history

  1. Received: July 1, 2021
  2. Preprint posted: July 6, 2021 (view preprint)
  3. Accepted: February 16, 2022
  4. Accepted Manuscript published: February 17, 2022 (version 1)
  5. Version of Record published: March 1, 2022 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,925
    views
  • 438
    downloads
  • 22
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Dongjin R Lee
  2. Christopher Rhodes
  3. Apratim Mitra
  4. Yajun Zhang
  5. Dragan Maric
  6. Ryan K Dale
  7. Timothy J Petros
(2022)
Transcriptional heterogeneity of ventricular zone cells in the ganglionic eminences of the mouse forebrain
eLife 11:e71864.
https://doi.org/10.7554/eLife.71864

Share this article

https://doi.org/10.7554/eLife.71864

Further reading

    1. Developmental Biology
    2. Immunology and Inflammation
    Tobias Weinberger, Messerer Denise ... Christian Schulz
    Research Article

    Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.

    1. Cell Biology
    2. Developmental Biology
    Corey D Holman, Alexander P Sakers ... Patrick Seale
    Research Article

    The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.