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Existing analyses typically treat these modalities as synchronized features that can be translated in a static manner; however, the temporal delays that underpin cellular kinetics are intrinsic to dynamic biological systems. To address this limitation, we propose utilizing the \u201cmolecular asynchrony\u201d within regulatory hierarchies to determine the thermodynamic properties of individual cells. Here, we present SeqTag, a single-cell multiomics sequencing method that simultaneously profiles the transcriptome, chromatin accessibility, and histone modifications, supported by an analytical framework to identify asynchronous states across regulatory layers for characterization of single-cell kinetics. By measuring the epigenetic priming potential and remodeling rates during adult mouse oligodendrogenesis, we delineated a sequential program for bivalency resolution as maturing cells traverse Waddington\u2019s landscape. This process becomes increasingly decoupled with age, a change linked to a drift in progenitor cell-fate probabilities. By identifying entropy-driving regulatory elements, we characterized the aging-related decline in cell identity across various cell types and proposed a dynamic model linking static genetic variants to the risk of late-onset diseases. In summary, our integrated approach established a unified framework for employing multimodal single-cell genomics to model the kinetics of complex cellular processes.<\/jats:p>","DOI":"10.64898\/2026.06.02.729594","type":"posted-content","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:50:21Z","timestamp":1780681821000},"source":"Crossref","is-referenced-by-count":0,"title":["The molecular asynchrony of single cells"],"prefix":"10.64898","author":[{"given":"Boshi","family":"Fu","sequence":"first","affiliation":[{"name":"New York Genome Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Tan","sequence":"additional","affiliation":[{"name":"New York Genome Center, New York, NY, USA"},{"name":"Department of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenkun","family":"Cao","sequence":"additional","affiliation":[{"name":"New York Genome Center, New York, NY, USA"},{"name":"Department of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA"},{"name":"Physiology, Biophysics and Systems Biology Graduate Program, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhen","family":"Bai","sequence":"additional","affiliation":[{"name":"New York Genome Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Bai","sequence":"additional","affiliation":[{"name":"New York Genome Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Song","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4216-6562","authenticated-orcid":false,"given":"Chenxu","family":"Zhu","sequence":"additional","affiliation":[{"name":"New York Genome Center, New York, NY, USA"},{"name":"Department of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060813101680000_2026.06.02.729594v1.1","unstructured":"Waddington, C.H. 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