{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:31Z","timestamp":1785421651436,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,27]]},"group-title":"Genomics","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R01CA2722891"],"award-info":[{"award-number":["R01CA2722891"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"MacMillan Family Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background &amp; Aims<\/jats:title>\n                  <jats:p>Gastric epithelial cells maintain homeostasis through dynamic self-renewal mechanisms involving stem and progenitor cells; however, identifying them has been challenging. This study aims to identify stem cells of healthy gastric epithelium and cell type-specific regulators defining gastric epithelial homeostasis via single-nucleus multiome analysis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Ten unique gastric samples were collected from 8-12 week old wildtype mice. Isolated nuclei were subjected to simultaneous profiling of gene expression and chromatin accessibility. After quality control, 31,598 cells were analyzed with Seurat and Signac using weighted-nearest neighbors analysis for joint RNA and ATAC clustering. Furthermore, SCENIC+, MultiVelo, EpiCHAOS and Cell plasticity score were used to uncover gene regulatory networks, cell state dynamics and lineage trajectories.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Our analyses were validated by the identification of known regulators of stem-cell differentiation into mature cell types. More importantly, it revealed previously uncharacterized regulatory networks comprising novel transcription factor combinations that define cell identities, including\n                    <jats:italic>Ppara<\/jats:italic>\n                    ,\n                    <jats:italic>Pparg<\/jats:italic>\n                    ,\n                    <jats:italic>Arid5b<\/jats:italic>\n                    and\n                    <jats:italic>Sox5<\/jats:italic>\n                    as candidate regulators of parietal, foveolar, chief and neck cells, respectively. Further, our data support the identity of isthmus cells as stem-like cells of healthy gastric epithelium, as evidenced by epigenetic plasticity that simultaneously contains open chromatin states of all differentiated cell types in the absence of transcriptional reprogramming.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Consistent with Waddington\u2019s epigenetic landscape hypothesis, gastric epithelial homeostasis is controlled by orchestrated epigenetic and transcriptional programs. Contrary to the prevailing hypothesis, stem cells can be defined not by a separate epigenetic state but by epigenetic superposition of differentiated cell states. Future work is needed to define the universality of these results.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.23.720450","type":"posted-content","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:25:19Z","timestamp":1777350319000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-nucleus multiome sequencing identifies candidate regulators of mouse gastric epithelial homeostasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-7144","authenticated-orcid":false,"given":"Maith\u00ea Rocha","family":"Monteiro de Barros","sequence":"first","affiliation":[{"name":"Herbert and Florence Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA"},{"name":"New York Genome Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Bosch","sequence":"additional","affiliation":[{"name":"Tumorigenesis and Molecular Cancer Prevention Group, German 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