Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Creators
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1.
University of California, Los Angeles
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2.
Osaka University
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3.
California Institute of Technology
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4.
UCLA Health
Abstract
Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer's disease (AD) risk genes. CRISPR/Cas9–mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.
Additional Information
We thank F. Gao and the UCLA Neuroscience Genomics Core for assistance with RNA-seq, M. Gangwani for AAV delivery (Fig. 6F) and discussions, S. Cheong for help counting astrocytes (Fig. 1D), D. Geschwind for discussion about gene expression analysis, A. Huang and L. Wu for comments, and N. Okabe for IHC guidance. The sequencing core was supported partly by the Genetics, Genomics and Informatics Core of the Semel Institute of Neuroscience. Funding: B.S.K., J.S., F.E., and X.Y. were supported by the National Institutes of Health (NIH grants R01DA047444, R35NS111583, and R01AG0759655), an Allen Distinguished Investigator Award, a Paul G. Allen Frontiers Group advised grant of the Paul G. Allen Family Foundation, and the Ressler Family Foundation (B.S.K.). J.S.S. was supported by the National Science Foundation Graduate Research Fellowship Program (NSF-GRFP; DGE-2034835) and by a UCLA Eugene V. Cota-Robles Fellowship. A.K. and H.H. were supported by JSPS KAKENHI grants JP21K19335 (H.H.), JP20H00492 (H.H.), and JP20H03391 (A.K.); MEXT KAKENHI grant JP18H05416 (H.H.); AMED grant JP21dm0207117 (H.H.); and the Takeda Science Foundation, Japan (A.K., H.H.). V.G. was supported by the NIH (Pioneer Award DP1OD025535), the Vallee Foundation, the CZI Neurodegeneration Challenge Network, and the Beckman Institute for CLARITY, Optogenetics and Vector Engineering Research (CLOVER) for technology development and dissemination.Additional details
Identifiers
- Eprint ID
- 118282
- Resolver ID
- CaltechAUTHORS:20221209-478595000.5
Funding
- NIH
- R01DA047444
- NIH
- R35NS111583
- NIH
- R01AG0759655
- Paul G. Allen Family Foundation
- Ressler Family Foundation
- NSF Graduate Research Fellowship
- DGE-2034835
- UCLA
- Japan Society for the Promotion of Science (JSPS)
- JP21K19335
- Japan Society for the Promotion of Science (JSPS)
- JP20H00492
- Japan Society for the Promotion of Science (JSPS)
- JP20H03391
- Japan Society for the Promotion of Science (JSPS)
- JP18H05416
- Osaka University
- JP21dm0207117
- Takeda Science Foundation
- NIH
- DP1OD025535
- Vallee Foundation
- CZI Neurodegeneration Challenge Network
- Beckman Institute for CLARITY, Optogenetics and Vector Engineering Research
Dates
- Created
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2023-01-12Created from EPrint's datestamp field
- Updated
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2023-01-17Created from EPrint's last_modified field
Caltech Custom Metadata
- Caltech groups
- Division of Biology and Biological Engineering (BBE)