
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184075
10.21203/rs.3.rs-4814866/v1
10.21203/rs.3.rs-4814866
preprint
1
Article
Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping
Fan Rong https://orcid.org/0000-0001-7805-8059

Zhang Di
Rodríguez-Kirby Leslie
Lin Yingxin
Song Mengyi
Wang Li https://orcid.org/0000-0001-9510-6294

Wang Lijun https://orcid.org/0000-0001-5222-4506

Kanatani Shigeaki https://orcid.org/0000-0003-2226-4288

Jimenez-Beristain Tony
Dang Yonglong https://orcid.org/0000-0001-9705-5507

Zhong Mei
Kukanja Petra https://orcid.org/0000-0003-1228-5923

Wang Shaohui
Chen Xinyi https://orcid.org/0009-0008-8812-9189

Gao Fu
Wang Dejiang
Xu Hang
Lou Xing
Liu Yang https://orcid.org/0000-0003-1830-948X

Chen Jinmiao
Sestan Nenad https://orcid.org/0000-0003-0966-9619

Uhlen Per https://orcid.org/0000-0003-1446-1062

Kriegstein Arnold R. https://orcid.org/0000-0001-5742-2990

Zhao Hongyu https://orcid.org/0000-0003-1195-9607

Castelo-Branco Goncalo https://orcid.org/0000-0003-2247-9393

12 8 2024
rs.3.rs-4814866https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4814866/v1
nihpp-rs4814866v1.pdf
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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