Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

  1. Felipe Mora-Bermúdez
  2. Farhath Badsha
  3. Sabina Kanton
  4. J Gray Camp
  5. Benjamin Vernot
  6. Kathrin Köhler
  7. Birger Voigt
  8. Keisuke Okita
  9. Tomislav Maricic
  10. Zhisong He
  11. Robert Lachmann
  12. Svante Pääbo  Is a corresponding author
  13. Barbara Treutlein  Is a corresponding author
  14. Wieland B Huttner  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Max Planck Institute for Evolutionary Anthropology, Germany
  3. Kyoto University, Japan
  4. CAS-MPG Partner Institute for Computational Biology, China
  5. Technische Universität Dresden, Germany

Abstract

Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistochemistry, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution.

Article and author information

Author details

  1. Felipe Mora-Bermúdez

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Farhath Badsha

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sabina Kanton

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. J Gray Camp

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Benjamin Vernot

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Kathrin Köhler

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Birger Voigt

    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Keisuke Okita

    Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Tomislav Maricic

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhisong He

    CAS-MPG Partner Institute for Computational Biology, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Robert Lachmann

    Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Svante Pääbo

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    For correspondence
    paabo@eva.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
  13. Barbara Treutlein

    Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
    For correspondence
    barbara_treutlein@eva.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
  14. Wieland B Huttner

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    huttner@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4143-7201

Funding

Boehringer Ingelheim Fonds

  • Sabina Kanton

Paul G. Allen Family Foundation

  • Svante Pääbo

Deutsche Forschungsgemeinschaft (DFG, SFB 655, A2)

  • Wieland B Huttner

European Research Council (ERC, 250197)

  • Wieland B Huttner

DFG-Funded Center for Regenerative Therapies Dresden

  • Wieland B Huttner

Fonds der Chemischen Industrie

  • Wieland B Huttner

Max Planck Society

  • Svante Pääbo
  • Barbara Treutlein
  • Wieland B Huttner

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

Ethics

Animal experimentation: Mice were kept pathogen-free at the Biomedical Services Facility of the MPI-CBG. All experiments using mice were performed according to the German Animal Welfare Legislation. In addition, research was approved by the Institutional Review Board of the Max Planck Institute of Molecular Cell Biology and Genetics.

Human subjects: Human fetal brain tissue (11-13 weeks post conception (wpc)) was obtained with informed written maternal consent followed by elective pregnancy termination. Research involving human tissue was approved by the Ethical Review Committee of the Universitaetsklinikum Carl Gustav Carus of the Technische Universitaet Dresden. In addition, research was approved by the Institutional Review Board of the Max Planck Institute of Molecular Cell Biology and Genetics.

Copyright

© 2016, Mora-Bermúdez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 61,820
    views
  • 2,418
    downloads
  • 220
    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. Felipe Mora-Bermúdez
  2. Farhath Badsha
  3. Sabina Kanton
  4. J Gray Camp
  5. Benjamin Vernot
  6. Kathrin Köhler
  7. Birger Voigt
  8. Keisuke Okita
  9. Tomislav Maricic
  10. Zhisong He
  11. Robert Lachmann
  12. Svante Pääbo
  13. Barbara Treutlein
  14. Wieland B Huttner
(2016)
Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development
eLife 5:e18683.
https://doi.org/10.7554/eLife.18683

Share this article

https://doi.org/10.7554/eLife.18683

Further reading

    1. Cancer Biology
    2. Cell Biology
    Xiangning Bu, Nathanael Ashby ... Inhee Chung
    Research Article

    Cell crowding is a common microenvironmental factor influencing various disease processes, but its role in promoting cell invasiveness remains unclear. This study investigates the biomechanical changes induced by cell crowding, focusing on pro-invasive cell volume reduction in ductal carcinoma in situ (DCIS). Crowding specifically enhanced invasiveness in high-grade DCIS cells through significant volume reduction compared to hyperplasia-mimicking or normal cells. Mass spectrometry revealed that crowding selectively relocated ion channels, including TRPV4, to the plasma membrane in high-grade DCIS cells. TRPV4 inhibition triggered by crowding decreased intracellular calcium levels, reduced cell volume, and increased invasion and motility. During this process, TRPV4 membrane relocation primed the channel for later activation, compensating for calcium loss. Analyses of patient-derived breast cancer tissues confirmed that plasma membrane-associated TRPV4 is specific to high-grade DCIS and indicates the presence of a pro-invasive cell volume reduction mechanotransduction pathway. Hyperosmotic conditions and pharmacologic TRPV4 inhibition mimicked crowding-induced effects, while TRPV4 activation reversed them. Silencing TRPV4 diminished mechanotransduction in high-grade DCIS cells, reducing calcium depletion, volume reduction, and motility. This study uncovers a novel pro-invasive mechanotransduction pathway driven by cell crowding and identifies TRPV4 as a potential biomarker for predicting invasion risk in DCIS patients.

    1. Cell Biology
    Dan Wu, Venkateswararao Eeda ... Weidong Wang
    Research Article

    Overnutrition engenders the expansion of adipose tissue and the accumulation of immune cells, in particular, macrophages, in the adipose tissue, leading to chronic low-grade inflammation and insulin resistance. In obesity, several proinflammatory subpopulations of adipose tissue macrophages (ATMs) identified hitherto include the conventional ‘M1-like’ CD11C-expressing ATM and the newly discovered metabolically activated CD9-expressing ATM; however, the relationship among ATM subpopulations is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) is activated in the adipocytes and immune cells under obesity. It is unknown whether targeting IRE1α is capable of reversing insulin resistance and obesity and modulating the metabolically activated ATMs. We report that pharmacological inhibition of IRE1α RNase significantly ameliorates insulin resistance and glucose intolerance in male mice with diet-induced obesity. IRE1α inhibition also increases thermogenesis and energy expenditure, and hence protects against high fat diet-induced obesity. Our study shows that the ‘M1-like’ CD11c+ ATMs are largely overlapping with but yet non-identical to CD9+ ATMs in obese white adipose tissue. Notably, IRE1α inhibition diminishes the accumulation of obesity-induced metabolically activated ATMs and ‘M1-like’ ATMs, resulting in the curtailment of adipose inflammation and ensuing reactivation of thermogenesis, without augmentation of the alternatively activated M2 macrophage population. Our findings suggest the potential of targeting IRE1α for the therapeutic treatment of insulin resistance and obesity.