MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development

  1. Kanella Prodromidou  Is a corresponding author
  2. Ioannis S Vlachos
  3. Maria Gaitanou
  4. Georgia Kouroupi
  5. Artemis G Hatzigeorgiou
  6. Rebecca Matsas  Is a corresponding author
  1. Hellenic Pasteur Institute, Greece
  2. Beth Israel Deaconess Medical Center, United States
  3. DIANA-Lab, University of Thessaly, Greece

Abstract

Integrating differential RNA and miRNA expression during neuronal lineage induction of human embryonic stem cells we identified miR-934, a primate-specific miRNA that displays a stage-specific expression pattern during progenitor expansion and early neuron generation. We demonstrate the biological relevance of this finding by comparison with data from early to mid-gestation human cortical tissue. Further we find that miR-934 directly controls progenitor to neuroblast transition and impacts on neurite growth of newborn neurons. In agreement, miR-934 targets are involved in progenitor proliferation and neuronal differentiation whilst miR-934 inhibition results in profound global transcriptome changes associated with neurogenesis, axonogenesis, neuronal migration and neurotransmission. Interestingly, miR-934 inhibition affects the expression of genes associated with the subplate zone, a transient compartment most prominent in primates that emerges during early corticogenesis. Our data suggest that mir-934 is a novel regulator of early human neurogenesis with potential implications for a species-specific evolutionary role in brain function.

Data availability

Sequencing data have been deposited in GEO under accession code GSE101548. All data generated or analysed during this study are included in the manuscript and supporting files.

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

Article and author information

Author details

  1. Kanella Prodromidou

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    For correspondence
    kprodromidou@pasteur.gr
    Competing interests
    The authors declare that no competing interests exist.
  2. Ioannis S Vlachos

    Pathology, Beth Israel Deaconess Medical Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria Gaitanou

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    Competing interests
    The authors declare that no competing interests exist.
  4. Georgia Kouroupi

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    Competing interests
    The authors declare that no competing interests exist.
  5. Artemis G Hatzigeorgiou

    Department of Electrical & Computer Engineering, DIANA-Lab, University of Thessaly, Volos, Greece
    Competing interests
    The authors declare that no competing interests exist.
  6. Rebecca Matsas

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    For correspondence
    rmatsa@pasteur.gr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4027-348X

Funding

Ministry of Education and Religious Affairs, Sport and Culture (Greek General Secreteriat for Research and Technology Grant EXCELLENCE 2272)

  • Rebecca Matsas

Ministry of Education and Religious Affairs, Sport and Culture (Greek General Secreteriat for Research and Technology Grant MIS 5002486)

  • Rebecca Matsas

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

Ethics

Human subjects: All procedures for generation of human iPSCs were approved by the Scientific Council and Ethics Committee of Attikon University Hospital (Athens, Greece), which is one of the Mendelian forms of Parkinson's Disease clinical centers, and by the Hellenic Pasteur Institute Ethics Committee overlooking stem cell research. Informed consent was obtained from all donors before skin biopsy. Proc Natl Acad Sci U S A. 2017 May 2;114(18)

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: July 26, 2019
  2. Accepted: May 21, 2020
  3. Accepted Manuscript published: May 27, 2020 (version 1)
  4. Version of Record published: June 15, 2020 (version 2)

Copyright

© 2020, Prodromidou 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

  • 1,173
    Page views
  • 186
    Downloads
  • 6
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Kanella Prodromidou
  2. Ioannis S Vlachos
  3. Maria Gaitanou
  4. Georgia Kouroupi
  5. Artemis G Hatzigeorgiou
  6. Rebecca Matsas
(2020)
MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development
eLife 9:e50561.
https://doi.org/10.7554/eLife.50561

Further reading

    1. Cancer Biology
    2. Developmental Biology
    Maja Solman et al.
    Research Article Updated

    Gain-of-function mutations in the protein-tyrosine phosphatase SHP2 are the most frequently occurring mutations in sporadic juvenile myelomonocytic leukemia (JMML) and JMML-like myeloproliferative neoplasm (MPN) associated with Noonan syndrome (NS). Hematopoietic stem and progenitor cells (HSPCs) are the disease propagating cells of JMML. Here, we explored transcriptomes of HSPCs with SHP2 mutations derived from JMML patients and a novel NS zebrafish model. In addition to major NS traits, CRISPR/Cas9 knock-in Shp2D61G mutant zebrafish recapitulated a JMML-like MPN phenotype, including myeloid lineage hyperproliferation, ex vivo growth of myeloid colonies, and in vivo transplantability of HSPCs. Single-cell mRNA sequencing of HSPCs from Shp2D61G zebrafish embryos and bulk sequencing of HSPCs from JMML patients revealed an overlapping inflammatory gene expression pattern. Strikingly, an anti-inflammatory agent rescued JMML-like MPN in Shp2D61G zebrafish embryos. Our results indicate that a common inflammatory response was triggered in the HSPCs from sporadic JMML patients and syndromic NS zebrafish, which potentiated MPN and may represent a future target for JMML therapies.

    1. Developmental Biology
    Yulong Liu et al.
    Research Article

    Zebrafish are an established research organism that has made many contributions to our understanding of vertebrate tissue and organ development, yet there are still significant gaps in our understanding of the genes that regulate gonad development, sex, and reproduction. Unlike the development of many organs, such as the brain and heart that form during the first few days of development, zebrafish gonads do not begin to form until the larval stage (≥5 dpf). Thus, forward genetic screens have identified very few genes required for gonad development. In addition, bulk RNA sequencing studies which identify genes expressed in the gonads do not have the resolution necessary to define minor cell populations that may play significant roles in development and function of these organs. To overcome these limitations, we have used single-cell RNA sequencing to determine the transcriptomes of cells isolated from juvenile zebrafish ovaries. This resulted in the profiles of 10,658 germ cells and 14,431 somatic cells. Our germ cell data represents all developmental stages from germline stem cells to early meiotic oocytes. Our somatic cell data represents all known somatic cell types, including follicle cells, theca cells and ovarian stromal cells. Further analysis revealed an unexpected number of cell subpopulations within these broadly defined cell types. To further define their functional significance, we determined the location of these cell subpopulations within the ovary. Finally, we used gene knockout experiments to determine the roles of foxl2l and wnt9b for oocyte development and sex determination and/or differentiation, respectively. Our results reveal novel insights into zebrafish ovarian development and function and the transcriptome profiles will provide a valuable resource for future studies.