Cell-type specific developmental defects inPTEN-mutant cortical organoids converge on abnormal circuit activity Article Swipe
Martina Pigoni
,
Ana Uzquiano
,
Bruna Paulsen
,
Amanda J. Kedaigle
,
Sung Min Yang
,
Panagiotis Symvoulidis
,
Xian Adiconis
,
Silvia Velasco
,
Rafaela Sartore
,
Kwanho Kim
,
Ashley Tucewicz
,
Kalliopi Tsafou
,
Xin Jin
,
Lindy E. Barrett
,
Fei Chen
,
Ed Boyden
,
Aviv Regev
,
Joshua Z. Levin
,
Paola Arlotta
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.11.15.516664
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.11.15.516664
De novo heterozygous loss-of-function mutations in PTEN are strongly associated with Autism spectrum disorders (ASD); however, it is unclear how heterozygous mutations in this gene affects different cell types during human brain development, and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type-specific developmental events that are affected by heterozygous mutations in PTEN . We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics, and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.
Related Topics
Concepts
PTEN
Biology
Organoid
Phenotype
Cell type
Loss of heterozygosity
Transcriptome
Wild type
Mutation
Cell
Mutant
Cell biology
Neuroscience
Genetics
Gene
Signal transduction
PI3K/AKT/mTOR pathway
Gene expression
Allele
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.11.15.516664
- https://www.biorxiv.org/content/biorxiv/early/2022/11/16/2022.11.15.516664.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4309371924
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4309371924Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2022.11.15.516664Digital Object Identifier
- Title
-
Cell-type specific developmental defects inPTEN-mutant cortical organoids converge on abnormal circuit activityWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-11-16Full publication date if available
- Authors
-
Martina Pigoni, Ana Uzquiano, Bruna Paulsen, Amanda J. Kedaigle, Sung Min Yang, Panagiotis Symvoulidis, Xian Adiconis, Silvia Velasco, Rafaela Sartore, Kwanho Kim, Ashley Tucewicz, Kalliopi Tsafou, Xin Jin, Lindy E. Barrett, Fei Chen, Ed Boyden, Aviv Regev, Joshua Z. Levin, Paola ArlottaList of authors in order
- Landing page
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https://doi.org/10.1101/2022.11.15.516664Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2022/11/16/2022.11.15.516664.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2022/11/16/2022.11.15.516664.full.pdfDirect OA link when available
- Concepts
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PTEN, Biology, Organoid, Phenotype, Cell type, Loss of heterozygosity, Transcriptome, Wild type, Mutation, Cell, Mutant, Cell biology, Neuroscience, Genetics, Gene, Signal transduction, PI3K/AKT/mTOR pathway, Gene expression, AlleleTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1Per-year citation counts (last 5 years)
- References (count)
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54Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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