Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells

Gregory A Wasserman, Aleksander D Szymaniak, Anne C Hinds, Kazuko Yamamoto, Hirofumi Kamata, Nicole M S Smith, Kristie Hillard, Claudia Carrieri, Adam T Labadorf, Lee J Quinton, Xingbin Ai, Xaralabos Varelas, Felicia Chen, Joseph P Mizgerd, Alan Fine, Donal O'Carroll, Matthew R Jones

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

P-element-induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells. Isolation and next-generation sequencing of MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells. Mice lacking MIWI2 exhibited an altered balance of airway epithelial cells, demonstrating fewer multiciliated cells and an increase in club cells. During pneumococcal pneumonia, Miwi2-deficient mice exhibited increased expression of inflammatory mediators and increased immune cell recruitment, leading to enhanced bacterial clearance. Taken together, our data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. By demonstrating roles for MIWI2 in airway cell identity and pulmonary innate immunity, these studies elucidate unanticipated physiological functions for Piwi proteins in somatic tissues.

Original languageEnglish
Pages (from-to)3866-3876
Number of pages11
JournalJournal of Clinical Investigation
Issue number10
Early online date18 Sept 2017
Publication statusPublished - 2 Oct 2017

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Argonaute Proteins
  • Epithelial Cells
  • Female
  • Gene Expression Regulation
  • Immunity, Innate
  • Lung
  • Male
  • Mice
  • Mice, Knockout
  • Respiratory Mucosa
  • Journal Article


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