Academic Journal
Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency.
| Τίτλος: | Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency. |
|---|---|
| Συγγραφείς: | Miyata K; Division of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.; Cancer Cell Communication Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan., Yang L; Division of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan., Yang Y; Division of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan., Kumegawa K; Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan., Maruyama R; Division of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.; Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. |
| Πηγή: | Science advances [Sci Adv] 2026 Oct 09; Vol. 12 (41), pp. eaed7880. Date of Electronic Publication: 2026 Oct 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| Ιατρικοί όροι (MeSH): | Transcription Factors*/deficiency , Transcription Factors*/genetics , DNA-Binding Proteins*/deficiency , DNA-Binding Proteins*/genetics , Cell Lineage*/genetics , Genetic Heterogeneity* , Transcription, Genetic*, Multiomics ; Animals ; Humans ; Gene Expression Profiling ; Single-Cell Gene Expression Analysis ; Gene Expression Regulation, Neoplastic ; Single-Cell Analysis |
| Περίληψη: | Transcriptional heterogeneity drives malignant progression, yet how it emerges within tumors remains unclear. By combining genetic perturbation and lineage tracing with parallel single-cell multiomics, we tracked the consequences of ARID1A loss within individual clonal lineages. ARID1A deficiency increased transcriptional variability both within and across clones, recurrently giving rise to diverse transcriptional profiles that did not converge on a common, coordinated pattern. This variability was accompanied by broadened chromatin accessibility at normally silenced loci and depended on residual SMARCA4 activity. Clones in which this variability was prominent showed no growth advantage under standard conditions but were preferentially recovered under specific environmental stresses and during lung colonization, a context dependence consistent with bet-hedging. Our findings suggest that loss of an epigenetic regulator can promote tumor evolution by relaxing transcriptional constraints and widening the range of phenotypes accessible to a clonal lineage, rather than by imposing a single fixed phenotype. |
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| Substance Nomenclature: | 0 (Transcription Factors) 0 (DNA-Binding Proteins) 0 (ARID1A protein, human) |
| Entry Date(s): | Date Created: 20261007 Date Completed: 20261007 Latest Revision: 20261009 |
| Update Code: | 20261009 |
| PubMed Central ID: | PMC13644795 |
| DOI: | 10.1126/sciadv.aed7880 |
| PMID: | 42842673 |
| Βάση Δεδομένων: | MEDLINE |
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