1. Developmental Biology
  2. Genetics and Genomics

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
https://doi.org/10.7554/eLife.55474
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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).

Reviewing Editor

  1. Bernard Robaire, McGill University, Canada

Publication history

  1. Received: January 25, 2020
  2. Accepted: July 27, 2020
  3. Accepted Manuscript published: July 30, 2020 (version 1)
  4. Version of Record published: August 13, 2020 (version 2)
  5. Version of Record updated: August 19, 2020 (version 3)

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

  • 3,924
    Page views
  • 543
    Downloads
  • 24
    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. 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

Categories and tags

Research organism

Further reading

    1. Developmental Biology
    2. Evolutionary Biology

    Metamorphosis of memory circuits in Drosophila reveals a strategy for evolving a larval brain

    James W Truman, Jacquelyn Price ... Tzumin Lee
    Research Article

    We have focused on the mushroom bodies (MB) of Drosophila to determine how the larval circuits are formed and then transformed into those of the adult at metamorphosis. The adult MB has a core of thousands of Kenyon neurons; axons of the early-born g class form a medial lobe and those from later-born a'b' and ab classes form both medial and vertical lobes. The larva, however, hatches with only g neurons and forms a vertical lobe 'facsimile' using larval-specific axon branches from its g neurons. Computations by the MB involves MB input (MBINs) and output (MBONs) neurons that divide the lobes into discrete compartments. The larva has 10 such compartments while the adult MB has 16. We determined the fates of 28 of the 32 types of MBONs and MBINs that define the 10 larval compartments. Seven larval compartments are eventually incorporated into the adult MB; four of their larval MBINs die, while 12 MBINs/MBONs continue into the adult MB although with some compartment shifting. The remaining three larval compartments are larval specific, and their MBIN/MBONs trans-differentiate at metamorphosis, leaving the MB and joining other adult brain circuits. With the loss of the larval vertical lobe facsimile, the adult vertical lobes, are made de novo at metamorphosis, and their MBONs/MBINs are recruited from the pool of adult-specific cells. The combination of cell death, compartment shifting, trans-differentiation, and recruitment of new neurons result in no larval MBIN-MBON connections persisting through metamorphosis. At this simple level, then, we find no anatomical substrate for a memory trace persisting from larva to adult. For the neurons that trans-differentiate, our data suggest that their adult phenotypes are in line with their evolutionarily ancestral roles while their larval phenotypes are derived adaptations for the larval stage. These cells arise primarily within lineages that also produce permanent MBINs and MBONs, suggesting that larval specifying factors may allow information related to birth-order or sibling identity to be interpreted in a modified manner in these neurons to cause them to adopt a modified, larval phenotype. The loss of such factors at metamorphosis, though, would then allow these cells to adopt their ancestral phenotype in the adult system.

    1. Developmental Biology

    Sex-specific role of myostatin signaling in neonatal muscle growth, denervation atrophy, and neuromuscular contractures

    Marianne E Emmert, Parul Aggarwal ... Roger Cornwall
    Research Article Updated

    Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female but not male mice, despite inducing hypertrophy of normally innervated muscles in both sexes. Additionally, the MSTN-dependent impairment of longitudinal muscle growth after NBPI in female mice is associated with perturbation of 20S proteasome activity, but not through alterations in canonical MSTN signaling pathways. These findings reveal a sex dimorphism in the regulation of neonatal longitudinal muscle growth and contractures, thereby providing insights into contracture pathophysiology, identifying a potential muscle-specific therapeutic target for contracture prevention, and underscoring the importance of sex as a biological variable in the pathophysiology of neuromuscular disorders.

    1. Developmental Biology
    2. Genetics and Genomics

    Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality

    Ankit Sabharwal, Mark D Wishman ... Stephen C Ekker
    Research Advance Updated

    The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Previously, we used the gene-breaking transposon to create 1200 transgenic zebrafish strains tagging protein-coding genes (Ichino et al., 2020), including the lrpprc locus. Here, we present and characterize a new genetic revertible animal model that recapitulates components of Leigh Syndrome French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the LRPPRC gene, involved in mitochondrial mRNA polyadenylation and translation. lrpprc zebrafish homozygous mutants displayed biochemical and mitochondrial phenotypes similar to clinical manifestations observed in patients, including dysfunction in lipid homeostasis. We were able to rescue these phenotypes in the disease model using a liver-specific genetic model therapy, functionally demonstrating a previously under-recognized critical role for the liver in the pathophysiology of this disease.