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PreprintCited by 33Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationRNA and protein synthesis mechanisms

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Integrated transcriptome and proteome analysis in human brain organoids reveals posttranscriptional regulation of ribosomal genes

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Sidhaye, Jaydeep, Trepte, Philipp, Sepke, Natalie, Novatchkova, Maria, Schutzbier, Michael, Dürnberger, Gerhard, Mechtler, Karl, Knoblich, Jürgen A.·2022·eLife
DOI 10.1101/2022.10.07.511280PMC PMC10059687

Preprint — published as 10.7554/elife.85135

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Abstract

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using human telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons and performed cell class and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed modules of gene expression during human corticogenesis. Investigation of one such module uncovered mTOR-mediated regulation of translation of the 5’TOP element-enriched translation machinery in early progenitor cells. We show that in early progenitors partial inhibition of the translation of ribosomal genes prevents precocious translation of differentiation markers. Overall, our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.

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Metadata

Authors
Sidhaye, J., Trepte, P., Sepke, N., Novatchkova, M., Schutzbier, M., Dürnberger, G., Mechtler, K., & Knoblich, J. A.
Affiliations
Institute of Molecular Biotechnology (AT)
ORCID
Venue
eLife
Publisher
openRxiv
Published
2022-10-07
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2022.10.07.511280
PMC
PMC10059687
OpenAlex
W4361196629
Cited by
33
References
1
Citations by year
2026: 9 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 1
FWCI
3.73
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Molecular Biology Organization (EMBO long term fellowship (EMBO ALTF 794-2018))
  • Vienna Science and Technology Fund (project LS20-079)
  • Österreichischen Akademie der Wissenschaften
  • Austrian Science Fund (P35045-B, P33380 (FB), ERA-CAPS I 3686, P32054 (FB))
  • Bundesministerium für Bildung, Wissenschaft und Forschung
  • Horizon 2020 Framework Programme (Project Number 823839, EPIC-XS project number 823839, European Research Council (ERC) Advanced Grant (no. 695642 and no. 874769))
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
post-transcriptional regulation, ribosomal genes, human brain organoids, cortical development, neural progenitor cells, mTOR signaling, translational regulation, transcriptome-proteome integration, neuronal differentiation
MeSH terms
Brain, Humans, Organoids, Proteome, Neurogenesis, Transcriptome

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