Single-cell transcriptomics of a dynamic cell behavior in murine airways

  1. Sheldon JJ Kwok
  2. Daniel T Montoro
  3. Adam L Haber
  4. Seok-Hyun Yun  Is a corresponding author
  5. Vladimir Vinarsky  Is a corresponding author
  1. LASE Innovation Inc, United States
  2. Broad Institute, United States
  3. Harvard Medical School, United States
  4. Massachusetts General Hospital, United States

Abstract

Despite advances in high-dimensional cellular analysis, the molecular profiling of dynamic behaviors of cells in their native environment remains a major challenge. We present a method that allows us to couple physiological behaviors of cells in an intact murine tissue to deep molecular profiling of individual cells. This method enabled us to establish a novel molecular signature for a striking migratory cellular behavior following injury in murine airways.

Data availability

Sequencing data have been deposited in GEO under accession code GSE193954.

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

Article and author information

Author details

  1. Sheldon JJ Kwok

    LASE Innovation Inc, Cambridge, United States
    Competing interests
    Sheldon JJ Kwok, Currently an employee of and has financial interests in LASE Innovation Inc..
  2. Daniel T Montoro

    Broad Institute, Cambridge, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6222-2149
  3. Adam L Haber

    Broad Institute, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Seok-Hyun Yun

    Wellman Center for Photomedicine, Harvard Medical School, Cambridge, United States
    For correspondence
    seok-hyun_yun@hms.harvard.edu
    Competing interests
    Seok-Hyun Yun, Has financial interests in LASE Innovation Inc. that were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies..
  5. Vladimir Vinarsky

    Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States
    For correspondence
    vvinarsky@gmail.com
    Competing interests
    Vladimir Vinarsky, Currently an employee and has financial interest in Vertex Pharmaceuticals, Inc..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1141-6434

Funding

National Heart, Lung, and Blood Institute (5P01HL120839)

  • Seok-Hyun Yun

National Heart, Lung, and Blood Institute (5F32HL154638)

  • Daniel T Montoro

National Institute of Biomedical Imaging and Bioengineering (P41EB015903)

  • Seok-Hyun Yun

National Institute of Biomedical Imaging and Bioengineering (P41EB015903)

  • Seok-Hyun Yun

National Cancer Institute (R01CA192878)

  • Seok-Hyun Yun

National Heart, Lung, and Blood Institute (K08HL124298)

  • Vladimir Vinarsky

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 maintained in an Association for Assessment and Accreditation of Laboratory Animal Care-accredited animal facility at the Massachusetts General Hospital, and procedures were performed with Institutional Animal Care and Use Committee (IACUC)-approved protocol 2009N000119.

Reviewing Editor

  1. Murim Choi, Seoul National University, Republic of Korea

Version history

  1. Received: December 23, 2021
  2. Preprint posted: January 31, 2022 (view preprint)
  3. Accepted: April 20, 2023
  4. Accepted Manuscript published: April 21, 2023 (version 1)
  5. Version of Record published: May 11, 2023 (version 2)

Copyright

© 2023, Kwok 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

  • 1,338
    Page views
  • 151
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, 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. Sheldon JJ Kwok
  2. Daniel T Montoro
  3. Adam L Haber
  4. Seok-Hyun Yun
  5. Vladimir Vinarsky
(2023)
Single-cell transcriptomics of a dynamic cell behavior in murine airways
eLife 12:e76645.
https://doi.org/10.7554/eLife.76645

Further reading

    1. Developmental Biology
    2. Evolutionary Biology
    Kwi Shan Seah, Vinodkumar Saranathan
    Research Article

    The study of color patterns in the animal integument is a fundamental question in biology, with many lepidopteran species being exemplary models in this endeavor due to their relative simplicity and elegance. While significant advances have been made in unraveling the cellular and molecular basis of lepidopteran pigmentary coloration, the morphogenesis of wing scale nanostructures involved in structural color production is not well understood. Contemporary research on this topic largely focuses on a few nymphalid model taxa (e.g., Bicyclus, Heliconius), despite an overwhelming diversity in the hierarchical nanostructural organization of lepidopteran wing scales. Here, we present a time-resolved, comparative developmental study of hierarchical scale nanostructures in Parides eurimedes and five other papilionid species. Our results uphold the putative conserved role of F-actin bundles in acting as spacers between developing ridges, as previously documented in several nymphalid species. Interestingly, while ridges are developing in P. eurimedes, plasma membrane manifests irregular mesh-like crossribs characteristic of Papilionidae, which delineate the accretion of cuticle into rows of planar disks in between ridges. Once the ridges have grown, disintegrating F-actin bundles appear to reorganize into a network that supports the invagination of plasma membrane underlying the disks, subsequently forming an extruded honeycomb lattice. Our results uncover a previously undocumented role for F-actin in the morphogenesis of complex wing scale nanostructures, likely specific to Papilionidae.

    1. Developmental Biology
    2. Neuroscience
    Xiong Yang, Rong Wan ... Ke Tang
    Research Article

    The hippocampus executes crucial functions from declarative memory to adaptive behaviors associated with cognition and emotion. However, the mechanisms of how morphogenesis and functions along the hippocampal dorsoventral axis are differentiated and integrated are still largely unclear. Here, we show that Nr2f1 and Nr2f2 genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss of Nr2f2 results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency of Nr2f1 leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of both Nr2f genes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover, Nr2f1/2 may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating the Lhx5-Lhx2 axis. Our findings revealed a novel mechanism that Nr2f1 and Nr2f2 converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.