An atlas of cell types in the mammalian epididymis and vas deferens

  1. Vera D Rinaldi
  2. Elisa Donnard
  3. Kyle Gellatly
  4. Morten Rasmussen
  5. Alper Kucukural
  6. Onur Yukselen
  7. Manuel Garber
  8. Upasna Sharma
  9. Oliver J Rando  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. University of California Santa Cruz, United States

Abstract

Following testicular spermatogenesis, mammalian sperm continue to mature in a long epithelial tube known as the epididymis, which plays key roles in remodeling sperm protein, lipid, and RNA composition. To understand the roles for the epididymis in reproductive biology, we generated a single cell atlas of the murine epididymis and vas deferens. We recovered key epithelial cell types including principal cells, clear cells, and basal cells, along with associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Moreover, our data illuminate extensive regional specialization of principal cell populations across the length of the epididymis. In addition to region-specific specialization of principal cells, we find evidence for functionally specialized subpopulations of stromal cells, and, most notably, two distinct populations of clear cells. Our dataset extends on existing knowledge of epididymal biology, and provides a wealth of information on potential regulatory and signaling factors that bear future investigation.

Data availability

Data are available at GEO, Accession #GSE145443.

The following data sets were generated

Article and author information

Author details

  1. Vera D Rinaldi

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0051-1754
  2. Elisa Donnard

    Department of Bioinformatic and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8834-8110
  3. Kyle Gellatly

    Department of Bioinformatic and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Morten Rasmussen

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alper Kucukural

    Department of Bioinformatic and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9983-394X
  6. Onur Yukselen

    Department of Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Manuel Garber

    Department of Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8732-1293
  8. Upasna Sharma

    Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Oliver J Rando

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Oliver.Rando@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1516-9397

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD080224)

  • Vera D Rinaldi
  • Elisa Donnard
  • Kyle Gellatly
  • Morten Rasmussen
  • Alper Kucukural
  • Onur Yukselen
  • Manuel Garber
  • Oliver J Rando

NIH Office of the Director (1DP2AG066622)

  • Upasna Sharma

John Templeton Foundation (61350)

  • Vera D Rinaldi
  • Oliver J Rando

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

Ethics

Animal experimentation: All animal care and use procedures were in accordance with guidelines of the University of Massachusetts Medical School Institutional Animal Care and Use Committee (Protocol # A-1833-18).

Copyright

© 2020, Rinaldi 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

  • 5,853
    views
  • 754
    downloads
  • 60
    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. Vera D Rinaldi
  2. Elisa Donnard
  3. Kyle Gellatly
  4. Morten Rasmussen
  5. Alper Kucukural
  6. Onur Yukselen
  7. Manuel Garber
  8. Upasna Sharma
  9. Oliver J Rando
(2020)
An atlas of cell types in the mammalian epididymis and vas deferens
eLife 9:e55474.
https://doi.org/10.7554/eLife.55474

Share this article

https://doi.org/10.7554/eLife.55474

Further reading

    1. Cell Biology
    2. Developmental Biology
    Heungjin Ryu, Kibum Nam ... Jung-Hoon Park
    Research Article

    In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.

    1. Developmental Biology
    Michele Bertacchi, Gwendoline Maharaux ... Michèle Studer
    Research Article Updated

    The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic regions, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.