Host developmental niche competence limits pancreatic organogenesis despite transplantation of embryonic pancreatic progenitors

Host developmental niche competence limits pancreatic organogenesis despite transplantation of embryonic pancreatic progenitors | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Host developmental niche competence limits pancreatic organogenesis despite transplantation of embryonic pancreatic progenitors Zeynab Javanfekr Shahri, Atsushi Noda, Takuto Hayashi, Ching-Wei Liao, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9263975/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Whether developmentally competent pancreatic progenitors can restore pancreatic structure and metabolic function in a defective host environment remains unclear. Here, we used intraplacental transplantation to compare the fate of dissociated E12.5 mouse pancreatic bud cells in permissive non-knockout and Pdx1 -deficient mouse recipients. In non-knockout hosts, donor-derived cells contributed to endocrine, acinar, and ductal compartments, indicating multilineage developmental competence after transplantation. In contrast, transplantation into Pdx1 -deficient recipients did not restore detectable pancreatic organ formation, although some recipients showed detectable insulin and transient postnatal improvement in blood glucose, consistent with partial endocrine differentiation and metabolic support without organ-level rescue. These findings indicate that, under the donor preparation and transplantation conditions used here, donor developmental competence alone was not sufficient to restore detectable pancreatic organ formation in Pdx1 -deficient recipients and support the interpretation that host developmental niche competence is a major limiting factor in this model. In parallel, analysis of published single-cell RNA-sequencing datasets, together with flow-cytometric validation, identified EPCAM as a practical reporter-independent surface marker labeling a large fraction of the PDX1 + epithelial compartment in the E12.5 pancreatic bud. Together, these results highlight the importance of host niche competence and provide a practical strategy for enriching embryonic pancreatic epithelial progenitor-containing populations. Biological sciences/Cell biology Biological sciences/Developmental biology Biological sciences/Stem cells pancreatic organogenesis developmental niche intraplacental transplantation pancreatic progenitors metabolic rescue Epcam pancreatic regeneration type 1 diabetes Full Text Additional Declarations No competing interests reported. Supplementary Files PDFSupFig.pdf Suptable1.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 26 Apr, 2026 Reviewers agreed at journal 19 Apr, 2026 Reviewers invited by journal 19 Apr, 2026 Editor assigned by journal 01 Apr, 2026 Submission checks completed at journal 01 Apr, 2026 First submitted to journal 30 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9263975","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":629769052,"identity":"1b9864df-d4e8-4f4f-9da3-5688fabe0df9","order_by":0,"name":"Zeynab Javanfekr Shahri","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Zeynab","middleName":"Javanfekr","lastName":"Shahri","suffix":""},{"id":629769054,"identity":"c0aee3e2-bd32-4080-824d-3d44e7093f69","order_by":1,"name":"Atsushi Noda","email":"","orcid":"","institution":"University of 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developmental niche, intraplacental transplantation, pancreatic progenitors, metabolic rescue, Epcam, pancreatic regeneration, type 1 diabetes","lastPublishedDoi":"10.21203/rs.3.rs-9263975/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9263975/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWhether developmentally competent pancreatic progenitors can restore pancreatic structure and metabolic function in a defective host environment remains unclear. Here, we used intraplacental transplantation to compare the fate of dissociated E12.5 mouse pancreatic bud cells in permissive non-knockout and \u003cem\u003ePdx1\u003c/em\u003e-deficient mouse recipients. In non-knockout hosts, donor-derived cells contributed to endocrine, acinar, and ductal compartments, indicating multilineage developmental competence after transplantation. In contrast, transplantation into \u003cem\u003ePdx1\u003c/em\u003e-deficient recipients did not restore detectable pancreatic organ formation, although some recipients showed detectable insulin and transient postnatal improvement in blood glucose, consistent with partial endocrine differentiation and metabolic support without organ-level rescue. These findings indicate that, under the donor preparation and transplantation conditions used here, donor developmental competence alone was not sufficient to restore detectable pancreatic organ formation in \u003cem\u003ePdx1\u003c/em\u003e-deficient recipients and support the interpretation that host developmental niche competence is a major limiting factor in this model. In parallel, analysis of published single-cell RNA-sequencing datasets, together with flow-cytometric validation, identified EPCAM as a practical reporter-independent surface marker labeling a large fraction of the PDX1\u003csup\u003e+\u003c/sup\u003e epithelial compartment in the E12.5 pancreatic bud. 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