Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium

Nicolette M. Johnson, Louis R. Parham, Jeeyoon Na, Keara E. Monaghan, Hannah M. Kolev, Alena Klochkova, Melissa S. Kim, Charles H. Danan, Zvi Cramer, Lauren A. Simon, Kaitlyn E. Naughton, Stephanie Adams-Tzivelekidis, Yuhua Tian, Patrick A. Williams, N. Adrian Leu, Simone Sidoli, Kelly A. Whelan, Ning Li, Christopher J. Lengner, Kathryn E. Hamilton

Research output: Contribution to journalArticlepeer-review

Abstract

The intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports a model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes to epithelial regeneration upon ablation of injury-sensitive stem cells. However, such facultative stem cell activity is rare within secretory populations. Here, we ask whether specific functional properties predict facultative stem cell activity. We utilize in vivo labeling combined with ex vivo organoid formation assays to evaluate how cell age and autophagic state contribute to facultative stem cell activity within secretory lineages. Strikingly, we find that cell age (time elapsed since cell cycle exit) does not correlate with secretory cell plasticity. Instead, high autophagic vesicle content predicts plasticity and resistance to DNA damaging injury independently of cell lineage. Our findings indicate that autophagic status prior to injury serves as a lineage-agnostic marker for the prospective identification of facultative stem cells.

Original languageEnglish (US)
Article numbere55209
JournalEMBO Reports
Volume23
Issue number11
DOIs
StatePublished - Nov 7 2022

Keywords

  • autophagy
  • facultative stem cell
  • organoid formation
  • paligenosis
  • regeneration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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