@article{beed298acd0149c4a9be909ef6812ddd,
title = "Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium",
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.",
keywords = "autophagy, facultative stem cell, organoid formation, paligenosis, regeneration",
author = "Johnson, {Nicolette M.} and Parham, {Louis R.} and Jeeyoon Na and Monaghan, {Keara E.} and Kolev, {Hannah M.} and Alena Klochkova and Kim, {Melissa S.} and Danan, {Charles H.} and Zvi Cramer and Simon, {Lauren A.} and Naughton, {Kaitlyn E.} and Stephanie Adams-Tzivelekidis and Yuhua Tian and Williams, {Patrick A.} and Leu, {N. Adrian} and Simone Sidoli and Whelan, {Kelly A.} and Ning Li and Lengner, {Christopher J.} and Hamilton, {Kathryn E.}",
note = "Funding Information: The authors thank David Speicher of the Wistar Institute, Dr. Kai Tan and lab (Children's Hospital of Philadelphia, and the following core facilities: CHOP Flow Core, Penn Flow Core, Center for Molecular Studies in Digestive and Liver Diseases (NIH P30‐DK050306) Molecular Pathology and Imaging Core, Penn Vet Imaging Core (Gordon Ruthel)). This work was supported by the following: NIH F31AI150224 (NMJ), NIH F31‐DK124956 (LRP), NIH R01DK12115 (KAW), NIH R01‐DK106309 (CJL), the State of Pennsylvania Commonwealth Research Enhancement Foundation (CURE) Health Research Formula Fund (HRFF) (CJL), NIH R01‐DK124369 (KEH), and Children's Hospital of Philadelphia Institutional Development Funds and Gastrointestinal Epithelium Modeling Program (KEH). Simone Sidoli gratefully acknowledges the Leukemia Research Foundation (Hollis Brownstein New Investigator Research Grant), American Federation for Aging Research (Sagol Network GerOmics award), Relay Therapeutics, Merck, and the NIH Office of the Director (1S10OD030286‐01). Funding Information: The authors thank David Speicher of the Wistar Institute, Dr. Kai Tan and lab (Children's Hospital of Philadelphia, and the following core facilities: CHOP Flow Core, Penn Flow Core, Center for Molecular Studies in Digestive and Liver Diseases (NIH P30-DK050306) Molecular Pathology and Imaging Core, Penn Vet Imaging Core (Gordon Ruthel)). This work was supported by the following: NIH F31AI150224 (NMJ), NIH F31-DK124956 (LRP), NIH R01DK12115 (KAW), NIH R01-DK106309 (CJL), the State of Pennsylvania Commonwealth Research Enhancement Foundation (CURE) Health Research Formula Fund (HRFF) (CJL), NIH R01-DK124369 (KEH), and Children's Hospital of Philadelphia Institutional Development Funds and Gastrointestinal Epithelium Modeling Program (KEH). Simone Sidoli gratefully acknowledges the Leukemia Research Foundation (Hollis Brownstein New Investigator Research Grant), American Federation for Aging Research (Sagol Network GerOmics award), Relay Therapeutics, Merck, and the NIH Office of the Director (1S10OD030286-01). Publisher Copyright: {\textcopyright} 2022 The Authors.",
year = "2022",
month = nov,
day = "7",
doi = "10.15252/embr.202255209",
language = "English (US)",
volume = "23",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "11",
}