@article{MA2022604,
  title = {Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury},
  journal = {Gastroenterology},
  volume = {162},
  number = {2},
  pages = {604-620.e20},
  year = {2022},
  issn = {0016-5085},
  doi = {https://doi.org/10.1053/j.gastro.2021.10.027},
  url = {https://www.sciencedirect.com/science/article/pii/S0016508521036659},
  author = {Zhibo Ma and Nikki K. Lytle and Bob Chen and Nidhi Jyotsana and Sammy Weiser Novak and Charles J. Cho and Leah Caplan and Olivia Ben-Levy and Abigail C. Neininger and Dylan T. Burnette and Vincent Q. Trinh and Marcus C.B. Tan and Emilee A. Patterson and Rafael {Arrojo e Drigo} and Rajshekhar R. Giraddi and Cynthia Ramos and Anna L. Means and Ichiro Matsumoto and Uri Manor and Jason C. Mills and James R. Goldenring and Ken S. Lau and Geoffrey M. Wahl and Kathleen E. DelGiorno},
  keywords = {ADM, Plasticity, Paligenosis, Tuft Cells, Enteroendocrine Cells},
  abstract = {Background & Aims
  Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression.
  Methods
  Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining.
  Results
  scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype.
  Conclusions
  Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.}
}

{"_id":"EDQHvJBk4poaWLisi","bibbaseid":"ma-lytle-chen-jyotsana-novak-cho-caplan-benlevy-etal-singlecelltranscriptomicsrevealsaconservedmetaplasiaprograminpancreaticinjury-2022","author_short":["Ma, Z.","Lytle, N. K.","Chen, B.","Jyotsana, N.","Novak, S. W.","Cho, C. J.","Caplan, L.","Ben-Levy, O.","Neininger, A. C.","Burnette, D. T.","Trinh, V. Q.","Tan, M. C.","Patterson, E. A.","Arrojo e Drigo, R.","Giraddi, R. R.","Ramos, C.","Means, A. L.","Matsumoto, I.","Manor, U.","Mills, J. C.","Goldenring, J. R.","Lau, K. S.","Wahl, G. M.","DelGiorno, K. E."],"bibdata":{"bibtype":"article","type":"article","title":"Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury","journal":"Gastroenterology","volume":"162","number":"2","pages":"604-620.e20","year":"2022","issn":"0016-5085","doi":"https://doi.org/10.1053/j.gastro.2021.10.027","url":"https://www.sciencedirect.com/science/article/pii/S0016508521036659","author":[{"firstnames":["Zhibo"],"propositions":[],"lastnames":["Ma"],"suffixes":[]},{"firstnames":["Nikki","K."],"propositions":[],"lastnames":["Lytle"],"suffixes":[]},{"firstnames":["Bob"],"propositions":[],"lastnames":["Chen"],"suffixes":[]},{"firstnames":["Nidhi"],"propositions":[],"lastnames":["Jyotsana"],"suffixes":[]},{"firstnames":["Sammy","Weiser"],"propositions":[],"lastnames":["Novak"],"suffixes":[]},{"firstnames":["Charles","J."],"propositions":[],"lastnames":["Cho"],"suffixes":[]},{"firstnames":["Leah"],"propositions":[],"lastnames":["Caplan"],"suffixes":[]},{"firstnames":["Olivia"],"propositions":[],"lastnames":["Ben-Levy"],"suffixes":[]},{"firstnames":["Abigail","C."],"propositions":[],"lastnames":["Neininger"],"suffixes":[]},{"firstnames":["Dylan","T."],"propositions":[],"lastnames":["Burnette"],"suffixes":[]},{"firstnames":["Vincent","Q."],"propositions":[],"lastnames":["Trinh"],"suffixes":[]},{"firstnames":["Marcus","C.B."],"propositions":[],"lastnames":["Tan"],"suffixes":[]},{"firstnames":["Emilee","A."],"propositions":[],"lastnames":["Patterson"],"suffixes":[]},{"firstnames":["Rafael"],"propositions":[],"lastnames":["Arrojo e Drigo"],"suffixes":[]},{"firstnames":["Rajshekhar","R."],"propositions":[],"lastnames":["Giraddi"],"suffixes":[]},{"firstnames":["Cynthia"],"propositions":[],"lastnames":["Ramos"],"suffixes":[]},{"firstnames":["Anna","L."],"propositions":[],"lastnames":["Means"],"suffixes":[]},{"firstnames":["Ichiro"],"propositions":[],"lastnames":["Matsumoto"],"suffixes":[]},{"firstnames":["Uri"],"propositions":[],"lastnames":["Manor"],"suffixes":[]},{"firstnames":["Jason","C."],"propositions":[],"lastnames":["Mills"],"suffixes":[]},{"firstnames":["James","R."],"propositions":[],"lastnames":["Goldenring"],"suffixes":[]},{"firstnames":["Ken","S."],"propositions":[],"lastnames":["Lau"],"suffixes":[]},{"firstnames":["Geoffrey","M."],"propositions":[],"lastnames":["Wahl"],"suffixes":[]},{"firstnames":["Kathleen","E."],"propositions":[],"lastnames":["DelGiorno"],"suffixes":[]}],"keywords":"ADM, Plasticity, Paligenosis, Tuft Cells, Enteroendocrine Cells","abstract":"Background & Aims Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression. Methods Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining. Results scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype. Conclusions Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.","bibtex":"@article{MA2022604,\r\n title = {Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury},\r\n journal = {Gastroenterology},\r\n volume = {162},\r\n number = {2},\r\n pages = {604-620.e20},\r\n year = {2022},\r\n issn = {0016-5085},\r\n doi = {https://doi.org/10.1053/j.gastro.2021.10.027},\r\n url = {https://www.sciencedirect.com/science/article/pii/S0016508521036659},\r\n author = {Zhibo Ma and Nikki K. Lytle and Bob Chen and Nidhi Jyotsana and Sammy Weiser Novak and Charles J. Cho and Leah Caplan and Olivia Ben-Levy and Abigail C. Neininger and Dylan T. Burnette and Vincent Q. Trinh and Marcus C.B. Tan and Emilee A. Patterson and Rafael {Arrojo e Drigo} and Rajshekhar R. Giraddi and Cynthia Ramos and Anna L. Means and Ichiro Matsumoto and Uri Manor and Jason C. Mills and James R. Goldenring and Ken S. Lau and Geoffrey M. Wahl and Kathleen E. DelGiorno},\r\n keywords = {ADM, Plasticity, Paligenosis, Tuft Cells, Enteroendocrine Cells},\r\n abstract = {Background & Aims\r\n Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression.\r\n Methods\r\n Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining.\r\n Results\r\n scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype.\r\n Conclusions\r\n Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.}\r\n}\r\n\r\n","author_short":["Ma, Z.","Lytle, N. K.","Chen, B.","Jyotsana, N.","Novak, S. W.","Cho, C. J.","Caplan, L.","Ben-Levy, O.","Neininger, A. C.","Burnette, D. T.","Trinh, V. Q.","Tan, M. C.","Patterson, E. A.","Arrojo e Drigo, R.","Giraddi, R. R.","Ramos, C.","Means, A. L.","Matsumoto, I.","Manor, U.","Mills, J. C.","Goldenring, J. R.","Lau, K. S.","Wahl, G. M.","DelGiorno, K. E."],"key":"MA2022604","id":"MA2022604","bibbaseid":"ma-lytle-chen-jyotsana-novak-cho-caplan-benlevy-etal-singlecelltranscriptomicsrevealsaconservedmetaplasiaprograminpancreaticinjury-2022","role":"author","urls":{"Paper":"https://www.sciencedirect.com/science/article/pii/S0016508521036659"},"keyword":["ADM","Plasticity","Paligenosis","Tuft Cells","Enteroendocrine Cells"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://github.com/salkmanorlab/manor_publications/raw/main/manorlab_pubs.bib","dataSources":["edXsq84pNeYoA6wo6","dr3nCm3wyZkR7nFZf"],"keywords":["adm","plasticity","paligenosis","tuft cells","enteroendocrine cells"],"search_terms":["single","cell","transcriptomics","reveals","conserved","metaplasia","program","pancreatic","injury","ma","lytle","chen","jyotsana","novak","cho","caplan","ben-levy","neininger","burnette","trinh","tan","patterson","arrojo e drigo","giraddi","ramos","means","matsumoto","manor","mills","goldenring","lau","wahl","delgiorno"],"title":"Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury","year":2022}