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A self\u2010renewing monolayer of primary murine colonic epithelial cells is formed over a soft, transparent hydrogel matrix for the scalable analysis of intracellular Ca<jats:sup>2+<\/jats:sup> transients. Cultures that are enriched for stem\/proliferative cells exhibit repetitive, high frequency (\u224825 peaks h<jats:sup>\u22121<\/jats:sup>), and short pulse width (\u224825 s) Ca<jats:sup>2+<\/jats:sup> transients. Upon cell differentiation the transient frequency declines by 50% and pulse width widens by 200%. Metabolites and growth factors that are known to modulate stem cell proliferation and differentiation through Wnt and Notch signaling pathways, including CHIR\u201099021, N\u2010[(3,5\u2010Difluorophenyl)acetyl]\u2010L\u2010alanyl\u20102\u2010phenylglycine\u20101,1\u2010dimethylethyl ester (DAPT), bone morphogenetic proteins (BMPs), and butyrate, also modulate Ca<jats:sup>2+<\/jats:sup> oscillation patterns in a consistent manner. Increasing the stiffness of the supportive matrix from 200 Pa to 3 GPa shifts Ca<jats:sup>2+<\/jats:sup> transient patterns toward those resembling differentiated cells. The ability to monitor Ca<jats:sup>2+<\/jats:sup> oscillations with the spatial and temporal resolution offered by this platform, combined with its amenability to high\u2010content screens, provides a powerful tool for investigating real\u2010time communication within a wide range of primary tissues in addition to the colonic epithelium.<\/jats:p>","DOI":"10.1002\/adhm.202101318","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T13:56:52Z","timestamp":1631455012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Stem\/Proliferative and Differentiated Cells within Primary Murine Colonic Epithelium Display Distinct Intracellular Free Ca<sup>2+<\/sup> Signal Codes"],"prefix":"10.1002","volume":"10","author":[{"given":"Sebastian","family":"Mestril","sequence":"first","affiliation":[{"name":"Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raehyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Hinman","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn M.","family":"Gomez","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Chapel Hill NC 27599 USA"},{"name":"Department of Pharmacology University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-768X","authenticated-orcid":false,"given":"Nancy L.","family":"Allbritton","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-12457-1_1"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2015.08.006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/aabb18"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.10.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.03.003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.308"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"a006023","DOI":"10.1101\/cshperspect.a006023","author":"Kuo I. 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