{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:16:24Z","timestamp":1768515384350,"version":"3.49.0"},"posted":{"date-parts":[[2024,8,30]]},"group-title":"Cancer Biology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Dclk1<\/jats:italic>\n                  expression defines a rare population of cells in the normal pancreas whose frequency is increased at early stages of pancreatic tumorigenesis. The identity and the precise roles of\n                  <jats:italic>Dclk1<\/jats:italic>\n                  expressing cells in pancreas have been matter of debate, although evidence suggests their involvement in a number of key functions, including regeneration and neoplasia. We employed a recently developed Dclk1 reporter mouse model and single cell RNAseq analysis to define\n                  <jats:italic>Dclk1<\/jats:italic>\n                  expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas,\n                  <jats:italic>Dclk1<\/jats:italic>\n                  epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia,\n                  <jats:italic>Dclk1<\/jats:italic>\n                  expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells are predominant. These two cell populations play opposing roles in pancreatic neoplasia, with Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  ADM-like cells sustaining tumor growth while Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  tuft-like cells requires the activation of the transcription factor SPIB and is further supported by a cellular paracrine loop involving cancer group 2 innate lymphoid cells (ILC2) and cancer activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  tuft-like cells release angiotensinogen that plays protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  cells in normal pancreas and unveils a protective axis against pancreatic neoplasia, involving CAFs, ILC2 and Dclk1\n                  <jats:sup>+<\/jats:sup>\n                  tuft-like cells, which ultimately results in angiotensinogen release.\n                <\/jats:p>","DOI":"10.1101\/2024.08.30.610508","type":"posted-content","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T23:30:18Z","timestamp":1725060618000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulatory network analysis of\n                  <i>Dclk1<\/i>\n                  gene expression reveals a tuft cell-ILC2 axis that inhibits pancreatic tumor progression"],"prefix":"10.64898","author":[{"given":"Giovanni","family":"Valenti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1469-4704","authenticated-orcid":false,"given":"Pasquale","family":"Laise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feijing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuo","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Vasciaveo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Sunagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Middelhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Nienh\u00fcser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermanno","family":"Malagola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoku","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina 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