{"doi":"10.1002/adhm.202101318","title":"Stem/Proliferative and Differentiated Cells within Primary Murine Colonic Epithelium Display Distinct Intracellular Free Ca<sup>2+</sup> Signal Codes","abstract":"Abstract The second messenger, intracellular free calcium (Ca 2+ ), acts to transduce mitogenic and differentiation signals incoming to the colonic epithelium. A self‐renewing monolayer of primary murine colonic epithelial cells is formed over a soft, transparent hydrogel matrix for the scalable analysis of intracellular Ca 2+ transients. Cultures that are enriched for stem/proliferative cells exhibit repetitive, high frequency (≈25 peaks h −1 ), and short pulse width (≈25 s) Ca 2+ 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‐99021, N‐[(3,5‐Difluorophenyl)acetyl]‐L‐alanyl‐2‐phenylglycine‐1,1‐dimethylethyl ester (DAPT), bone morphogenetic proteins (BMPs), and butyrate, also modulate Ca 2+ oscillation patterns in a consistent manner. Increasing the stiffness of the supportive matrix from 200 Pa to 3 GPa shifts Ca 2+ transient patterns toward those resembling differentiated cells. The ability to monitor Ca 2+ oscillations with the spatial and temporal resolution offered by this platform, combined with its amenability to high‐content screens, provides a powerful tool for investigating real‐time communication within a wide range of primary tissues in addition to the colonic epithelium.","journal":"Advanced Healthcare Materials","year":2021,"id":207801,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490425,"name":"Raehyun Kim","orcid":"0000-0002-8796-2004","position":1,"is_corresponding":false},{"id":490424,"name":"Samuel S. Hinman","orcid":"0000-0002-7727-0450","position":2,"is_corresponding":false},{"id":256023,"name":"Shawn M. Gomez","orcid":"0000-0002-8251-4552","position":3,"is_corresponding":false},{"id":284766,"name":"Nancy L. Allbritton","orcid":"0000-0002-9242-768X","position":4,"is_corresponding":false},{"id":794412,"name":"Sebastian Mestril","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:51:53.662668Z","pmid":"34510822","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}