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Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium
Author(s) -
Johnson Nicolette M,
Parham Louis R,
Na Jeeyoon,
Monaghan Keara E,
Kolev Hannah M,
Klochkova Alena,
Kim Melissa S,
Danan Charles H,
Cramer Zvi,
Simon Lauren A,
Naughton Kaitlyn E,
AdamsTzivelekidis Stephanie,
Tian Yuhua,
Williams Patrick A,
Leu N Adrian,
Sidoli Simone,
Whelan Kelly A,
Li Ning,
Lengner Christopher J,
Hamilton Kathryn E
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202255209
Subject(s) - stem cell , biology , microbiology and biotechnology , autophagy , facultative , genetics , apoptosis , botany
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.