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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,5,19]]},"abstract":"<jats:p>\n                    We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic protein (BMP) receptor 1A (BMPR1A)\/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3\n                    <jats:sup>bright+<\/jats:sup>\n                    -sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3\n                    <jats:sup>bright+<\/jats:sup>\n                    dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1\n                    <jats:sup>+<\/jats:sup>\n                    \/ALK3\n                    <jats:sup>bright+<\/jats:sup>\n                    populations (enriched in PDX1\n                    <jats:sup>+<\/jats:sup>\n                    \/ALK3\n                    <jats:sup>+<\/jats:sup>\n                    \/CAII\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells) differentiate into all pancreatic lineages, including functional \u03b2-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1\n                    <jats:sup>+<\/jats:sup>\n                    \/ALK3\n                    <jats:sup>+<\/jats:sup>\n                    \/CAII\n                    <jats:sup>\u2212<\/jats:sup>\n                    progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1918314117","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T21:36:27Z","timestamp":1588282587000},"page":"10876-10887","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-6151","authenticated-orcid":false,"given":"Mirza Muhammad Fahd","family":"Qadir","sequence":"first","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"\u00c1lvarez-Cubela","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Klein","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmijn","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Instituut voor Life Science &amp; Technology, Hanze University of Applied Sciences, 9747 AS Groningen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Mu\u00f1iz-Anquela","sequence":"additional","affiliation":[{"name":"Vrije Universiteit Medisch Centrum School of Medical Sciences, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9823-4312","authenticated-orcid":false,"given":"Yaisa B.","family":"Moreno-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Facultad de Medicina, Universidad Francisco de Vitoria, 28223 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lanzoni","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of Miami, Coral Gables, FL 33146;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Navarro-Rubio","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Facultad de Medicina, Universidad Francisco de Vitoria, 28223 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3954-0242","authenticated-orcid":false,"given":"Kevin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7372-9896","authenticated-orcid":false,"given":"David","family":"Sant","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Utah, Salt Lake City, UT 84108;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Ricordi","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Department of Biomedical Engineering, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"Department of Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Miami Miller School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Griswold","sequence":"additional","affiliation":[{"name":"The Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Luis","family":"Pastori","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"name":"The Dr. John T. Macdonald Foundation Department of Human Genetics, John P. 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