{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:48:41Z","timestamp":1785408521751,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,12]]},"group-title":"Systems Biology","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 AI139246"],"award-info":[{"award-number":["R01 AI139246"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI179910"],"award-info":[{"award-number":["R01 AI179910"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI165475"],"award-info":[{"award-number":["R01 AI165475"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R01 GM089771"],"award-info":[{"award-number":["R01 GM089771"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2107344"],"award-info":[{"award-number":["2107344"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,22]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Type I and III interferons (IFNs) are among the first lines of defense against viral infection, yet they are generally only produced by a tiny fraction of infected cells. Here, we show that cellular heterogeneity in IFN induction potential upon treatment with immunostimulatory RNA is not due to variability in sensing of stimuli but instead is shaped by heterogeneity in tonic cell signaling state. Using complementary single-cell approaches, we found that baseline variation in the c-Jun N-terminal kinase (JNK) and activator protein (AP)-1 transcription factor families correlated with\n                  <jats:italic>IFNL1<\/jats:italic>\n                  expression predisposition. We further show that drug-based inhibition of JNK signaling virtually eliminates the innate antiviral response to immunostimulatory RNA. Finally, we show that single cell heterogeneity in IFN induction potential is heritable and stably maintained over numerous generations. Together, our study emphasizes the influence of intrinsic variability in cell state on innate immune regulation and IFN induction heterogeneity.\n                <\/jats:p>","DOI":"10.64898\/2025.12.09.693293","type":"posted-content","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:40:26Z","timestamp":1765564826000},"source":"Crossref","is-referenced-by-count":2,"title":["Single-cell heterogeneity in interferon induction potential is heritable and governed by variation in cell state"],"prefix":"10.64898","author":[{"given":"Elizabeth A.","family":"Thayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Shipman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Rivera-Cardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-9517","authenticated-orcid":false,"given":"Tarun","family":"Mahajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Wen","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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