title: Developmental heterogeneity in DNA packaging patterns influences T-cell activation and transmigration.
abstract: Cellular differentiation programs are accompanied by large-scale changes in nuclear organization and gene expression. In this context, accompanying transitions in chromatin assembly that facilitates changes in gene expression and cell behavior in a developmental system are poorly understood. Here, we address this gap and map structural changes in chromatin organization during murine T-cell development, to describe an unusual heterogeneity in chromatin organization and associated functional correlates in T-cell lineage. Confocal imaging of DNA assembly in cells isolated from bone marrow, thymus and spleen reveal the emergence of heterogeneous patterns in DNA organization in mature T-cells following their exit from the thymus. The central DNA pattern dominated in immature precursor cells in the thymus whereas both central and peripheral DNA patterns were observed in naïve and memory cells in circulation. Naïve T-cells with central DNA patterns exhibited higher mechanical pliability in response to compressive loads in vitro and transmigration assays in vivo, and demonstrated accelerated expression of activation-induced marker CD69. T-cell activation was characterized by marked redistribution of DNA assembly to a central DNA pattern and increased nuclear size. Notably, heterogeneity in DNA patterns recovered in cells induced into quiescence in culture, suggesting an internal regulatory mechanism for chromatin reorganization. Taken together, our results uncover an important component of plasticity in nuclear organization, reflected in chromatin assembly, during T-cell development, differentiation and transmigration.
authors.affiliation: National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, Karnataka, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Gupta
authors.forename: Nimi
authors.initials: N
authors.lastname: Marcel
authors.forename: Shefali
authors.initials: S
authors.lastname: Talwar
authors.forename: Megha
authors.initials: M
authors.lastname: Garg
authors.forename: Indulaxmi
authors.initials: I
authors.lastname: R
authors.forename: Lakshmi R
authors.initials: LR
authors.lastname: Perumalsamy
authors.forename: Apurva
authors.initials: A
authors.lastname: Sarin
authors.forename: G V
authors.initials: GV
authors.lastname: Shivashankar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D015233:Models, Statistical; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002843:Chromatin; D004247:DNA; D037181:Lectins, C-Type; D000099192:CD69 Antigens