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Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping.
Zhang, Di; Rubio Rodríguez-Kirby, Leslie A; Lin, Yingxin; Song, Mengyi; Wang, Li; Wang, Lijun; Kanatani, Shigeaki; Jimenez-Beristain, Tony; Dang, Yonglong; Zhong, Mei; Kukanja, Petra; Wang, Shaohui; Chen, Xinyi Lisa; Gao, Fu; Wang, Dejiang; Xu, Hang; Lou, Xing; Liu, Yang; Chen, Jinmiao; Sestan, Nenad; Uhlén, Per; Kriegstein, Arnold; Zhao, Hongyu; Castelo-Branco, Gonçalo; Fan, Rong.
Afiliación
  • Zhang D; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
  • Rubio Rodríguez-Kirby LA; These authors contributed equally.
  • Lin Y; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Song M; These authors contributed equally.
  • Wang L; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Wang L; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco; San Francisco, CA 94143, USA.
  • Kanatani S; Department of Neurology, University of California San Francisco; San Francisco, CA 94143, USA.
  • Jimenez-Beristain T; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco; San Francisco, CA 94143, USA.
  • Dang Y; Department of Neurology, University of California San Francisco; San Francisco, CA 94143, USA.
  • Zhong M; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Kukanja P; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Wang S; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Chen XL; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Gao F; Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Wang D; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Xu H; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco; San Francisco, CA 94143, USA.
  • Lou X; Department of Neurology, University of California San Francisco; San Francisco, CA 94143, USA.
  • Liu Y; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Chen J; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
  • Sestan N; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
  • Uhlén P; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
  • Kriegstein A; Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
  • Zhao H; Binformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Castelo-Branco G; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
  • Fan R; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
bioRxiv ; 2024 Jul 28.
Article en En | MEDLINE | ID: mdl-39091821
ABSTRACT
The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos