Stepwise reorganization of chromosome conformation and nuclear organization during stem cell differentiation
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Le résumé fourni par la source
Abstract Nuclear organization is a fundamental feature of cell identity and cell fate determination. Compared with differentiated cells, pluripotent stem cells exhibit markedly distinct nuclear architecture at multiple levels, including chromosome folding, lamina association, histone modification landscapes and nuclear body organization. Although individual aspects of this reorganization have been characterized, how and in what order these features are remodeled as cells commit to a lineage remains poorly understood. Here, we temporally map nuclear reorganization across five stages of an in vitro differentiation system of human embryonic stem cells through definitive endoderm and hepatoblast intermediates into hepatocyte-like cells. By integrating Hi-C, RNA-seq, ATAC-seq, ChIP-seq, and CUT&RUN data, we establish a genome-wide framework linking structural, epigenetic, and transcriptional changes across differentiation. Combined with immunofluorescence imaging, chromosome painting, and liquid chromatin Hi-C (LC-Hi-C) we show that nuclear reorganization proceeds in a stepwise and temporally ordered manner through three major transitions. In the first transition, chromosomes condense into defined territories concurrent with transient anchoring of centromere-proximal regions to the nuclear periphery. In a second transition, active and inactive chromatin segregate, leading to stronger compartmentalization. This coincides with deposition and peripheralization of H3K9me2-marked chromatin and morphological changes in nuclear speckles, while chromatin conformation at speckle-associated regions stabilizes. In a third transition, after lineage-specific genes are activated, chromatin interactions globally stabilize, establishing a more stable nuclear architecture on top of these earlier large-scale structural rearrangements. Together, our results define a stepwise framework for nuclear reorganization during human embryonic stem cell differentiation and reveal that the transition from pluripotency to a differentiated state proceeds through coordinated, temporally ordered structural events.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Stepwise reorganization of chromosome conformation and nuclear organization during stem cell differentiation
- Date Crossref
- 18/09/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Howard Hughes Medical Institute pays non établi dans la noticeStructure de recherche
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University of Massachusetts Chan Medical School pays non établi dans la noticeUniversité ou école supérieure
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Massachusetts Institute of Technology Department of Physics pays non établi dans la noticeUniversité ou école supérieure
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IIT@MIT pays non établi dans la noticeStructure de recherche
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Department of Systems Biology pays non établi dans la noticeInstitution
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Department of Genomics and Computational Biology pays non établi dans la noticeInstitution
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Diabetes Center of Excellence pays non établi dans la noticeInstitution
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Program in Molecular Medicine pays non établi dans la noticeInstitution
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Institute for Medical Engineering and Science pays non établi dans la noticeStructure de recherche
Howard Hughes Medical Institute, University of Massachusetts Chan Medical School et Department of Physics — Massachusetts Institute of Technology, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.