Enhancer-driven gene regulatory network of forebrain human development provides insights into autism Article Swipe
Alexandre Jourdon
,
Jessica Mariani
,
Abhiram Natu
,
Feinan Wu
,
Boxun Li
,
Davide Capauto
,
Kevin Hagy
,
Scott Norton
,
Livia Tomasini
,
Alexias Safi
,
Anahita Amiri
,
Jeremy D. Schreiner
,
Cindy Khanh Nguyen
,
Neal M. Nolan
,
Matthew P. Nelson
,
Daniel M. Ramos
,
Michael E. Ward
,
Anna Szekely
,
James C. McPartland
,
Kevin A. Pelphrey
,
Pamela Ventola
,
Katarzyna Chawarska
,
Charlie A Gersbach
,
Gregory E. Crawford
,
Alexej Abyzov
,
Flora M. Vaccarino
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.06.555206
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.06.555206
Summary Cell differentiation is orchestrated by transcription factors (TFs) binding to enhancers, shaping gene regulatory networks that drive neuronal lineage specification. Deciphering these enhancer-driven networks in human forebrain development is essential for understanding the genetic basis of neurodevelopmental disorders. Through integrative epigenomic and transcriptomic analyses of human forebrain organoids derived from 10 individuals with autism spectrum disorder (ASD) and their neurotypical fathers, we constructed a comprehensive enhancer-driven gene regulatory network (GRN) of early neurodevelopment. This GRN revealed hierarchical regulatory transitions guiding neuronal differentiation and was experimentally validated via CRISPR interference (CRISPRi) and loss-of-function analyses. A subnetwork linked ASD-associated transcriptomic alterations to dysregulated TF activity, implicating FOXG1, BHLHE22, EOMES, and NEUROD2 as key regulators of excitatory neuron specification in macrocephalic ASD. These findings suggest that ASD disrupts enhancer-driven regulatory frameworks, altering neuronal cell fate decisions in the developing fetal brain.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.09.06.555206
- OA Status
- green
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386536845
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386536845Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.09.06.555206Digital Object Identifier
- Title
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Enhancer-driven gene regulatory network of forebrain human development provides insights into autismWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-09-08Full publication date if available
- Authors
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Alexandre Jourdon, Jessica Mariani, Abhiram Natu, Feinan Wu, Boxun Li, Davide Capauto, Kevin Hagy, Scott Norton, Livia Tomasini, Alexias Safi, Anahita Amiri, Jeremy D. Schreiner, Cindy Khanh Nguyen, Neal M. Nolan, Matthew P. Nelson, Daniel M. Ramos, Michael E. Ward, Anna Szekely, James C. McPartland, Kevin A. Pelphrey, Pamela Ventola, Katarzyna Chawarska, Charlie A Gersbach, Gregory E. Crawford, Alexej Abyzov, Flora M. VaccarinoList of authors in order
- Landing page
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https://doi.org/10.1101/2023.09.06.555206Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/12247993Direct OA link when available
- Concepts
-
Forebrain, Autism, Enhancer, Neuroscience, Psychology, Biology, Developmental psychology, Genetics, Gene, Transcription factor, Central nervous systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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63Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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