Integrated transcriptome and proteome analysis reveals posttranscriptional regulation of ribosomal genes in human brain organoids
Open Access
- 29 March 2023
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
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 posttranscriptional 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 proposes novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.Keywords
Funding Information
- Austrian Science Fund (Special Research Programme F7804-B and Stand-Alone grants P 35680 and P 35369)
- Horizon 2020 Framework Programme (European Research Council (ERC) Advanced Grant (no. 695642 and no. 874769))
- European Molecular Biology Organization (EMBO long term fellowship (EMBO ALTF 794-2018))
- Horizon 2020 Framework Programme (Marie Skłodowska-Curie fellowship agreement 841940)
- Horizon 2020 Framework Programme (Marie Skłodowska-Curie fellowship agreement 897137)
- Horizon 2020 Framework Programme (EPIC-XS, Project Number 823839)
- Vienna Science and Technology Fund (project LS20-079)
- Austrian Science Fund (ERA-CAPS I 3686)
- Austrian Science Fund (P33380 (FB))
- Austrian Science Fund (P32054 (FB))
- Austrian Science Fund (P35045-B)
- Austrian Academy of Sciences
- Austrian Federal Ministry of Education, Science and Research
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