Single-cell transcriptomics of a dynamic cell behavior in murine airways
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.
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Single-cell transcriptomics of dynamic cell behaviorsNCBI Gene Expression Omnibus, GSE193954.
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A single cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyteNCBI Gene Expression Omnibus, GSE102580.
Article and author information
Author details
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.
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.
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Further reading
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Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Using genetic approach in mice, we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.
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