Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration

Arvind Konkimalla, Satoshi Konishi, Yoshihiko Kobayashi, Preetish Kadur Lakshminarasimha Murthy, Lauren Macadlo, Ananya Mukherjee, Zachary Elmore, So Jin Kim, Ann Marie Pendergast, Patty J. Lee, Aravind Asokan, Lars Knudsen, Jose Javier Bravo-Cordero, Aleksandra Tata, Purushothama Rao Tata

Research output: Contribution to journalArticlepeer-review


Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basolateral organization of the AT2s and their establishment during development and remodeling after injury repair remain unknown. Thick tissue imaging and electron microscopy revealed that a single AT2 can have multiple apical domains that enface multiple alveoli. AT2s gradually establish multi-apical domains post-natally, and they are maintained throughout life. Lineage tracing, live imaging, and selective cell ablation revealed that AT2s dynamically reorganize multi-apical domains during injury repair. Single-cell transcriptome signatures of residual AT2s revealed changes in cytoskeleton and cell migration. Significantly, cigarette smoke and oncogene activation lead to dysregulation of multi-apical domains. We propose that the multi-apical domains of AT2s enable them to be poised to support the regeneration of a large array of alveolar sacs.

Original languageEnglish
Article number105114
Issue number10
StatePublished - 21 Oct 2022


  • Cell biology
  • Developmental biology
  • Stem cells research


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