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<p>Mammalian lung development requires coordinated gene regulation to drive lung bud formation, branching morphogenesis, proximal-distal patterning, and epithelial specification. While key transcriptional and signaling regulators are known, the epigenetic regulators are less well studied. Here, we identify the canonical BAF complex as essential for lung epithelial development. Complete loss of BAF complex function&#xa0;causes failure of lung formation, and selective deletion of ARID1A leads to loss of distal patterning and reduced alveolar type 1 (AT1) cell differentiation, with emergence of a highly proliferative cell state defined by joint activation of YAP and WNT signaling and loss of BMP response. Epigenomic analyses demonstrate broad failure of cell type-specific enhancer activation. Notably, exogenous BMP4 rescues distal differentiation in embryonic murine lung organoids, while YAP and WNT signaling require functional BAF complex. These data demonstrate a requirement for BAF complex activity during lung epithelial development and reveal a surprising differential specificity between signaling pathways.</p>

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Cell fate specification during respiratory development requires ARID1A-containing canonical BAF complex activity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

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  • Hyunwook Lee,
  • Abigail Jaquish,
  • Sharlene Fernandes,
  • Barbara Zhao,
  • Amber Elitz,
  • Kathleen Cook,
  • Sarah Trovillion,
  • Natalia Bottasso-Arias,
  • Simon J. Y. Han,
  • Samantha Goodwin,
  • Nicholas X. Russell,
  • Gerald Saunders,
  • Amanda L. Zacharias,
  • Samantha A. Brugmann,
  • Jeffrey A. Whitsett,
  • Debora Sinner,
  • Xin Sun,
  • Daniel T. Swarr,
  • William J. Zacharias

摘要

Mammalian lung development requires coordinated gene regulation to drive lung bud formation, branching morphogenesis, proximal-distal patterning, and epithelial specification. While key transcriptional and signaling regulators are known, the epigenetic regulators are less well studied. Here, we identify the canonical BAF complex as essential for lung epithelial development. Complete loss of BAF complex function causes failure of lung formation, and selective deletion of ARID1A leads to loss of distal patterning and reduced alveolar type 1 (AT1) cell differentiation, with emergence of a highly proliferative cell state defined by joint activation of YAP and WNT signaling and loss of BMP response. Epigenomic analyses demonstrate broad failure of cell type-specific enhancer activation. Notably, exogenous BMP4 rescues distal differentiation in embryonic murine lung organoids, while YAP and WNT signaling require functional BAF complex. These data demonstrate a requirement for BAF complex activity during lung epithelial development and reveal a surprising differential specificity between signaling pathways.