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Trans-omic profiling uncovers molecular controls of early human cerebral organoid formation.
- Source :
-
Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114219. Date of Electronic Publication: 2024 May 14. - Publication Year :
- 2024
-
Abstract
- Defining the molecular networks orchestrating human brain formation is crucial for understanding neurodevelopment and neurological disorders. Challenges in acquiring early brain tissue have incentivized the use of three-dimensional human pluripotent stem cell (hPSC)-derived neural organoids to recapitulate neurodevelopment. To elucidate the molecular programs that drive this highly dynamic process, here, we generate a comprehensive trans-omic map of the phosphoproteome, proteome, and transcriptome of the exit of pluripotency and neural differentiation toward human cerebral organoids (hCOs). These data reveal key phospho-signaling events and their convergence on transcriptional factors to regulate hCO formation. Comparative analysis with developing human and mouse embryos demonstrates the fidelity of our hCOs in modeling embryonic brain development. Finally, we demonstrate that biochemical modulation of AKT signaling can control hCO differentiation. Together, our data provide a comprehensive resource to study molecular controls in human embryonic brain development and provide a guide for the future development of hCO differentiation protocols.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Pluripotent Stem Cells metabolism
Pluripotent Stem Cells cytology
Proteome metabolism
Signal Transduction
Transcriptome genetics
Proteomics methods
Neurogenesis
Proto-Oncogene Proteins c-akt metabolism
Organoids metabolism
Cell Differentiation
Brain metabolism
Brain embryology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 38748874
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114219