Trans-omic profiling uncovers molecular controls of early human cerebral organoid formation

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 recap...

Full description

Saved in:

Bibliographic Details
Published in:	Cell reports (Cambridge) Vol. 43; no. 5; p. 114219
Main Authors:	Chen, Carissa, Lee, Scott, Zyner, Katherine G., Fernando, Milan, Nemeruck, Victoria, Wong, Emilie, Marshall, Lee L., Wark, Jesse R., Aryamanesh, Nader, Tam, Patrick P.L., Graham, Mark E., Gonzalez-Cordero, Anai, Yang, Pengyi
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 28-05-2024 Elsevier
Subjects:	Animals Brain - embryology Brain - metabolism Cell Differentiation CP: Neuroscience CP: Stem cell research human cerebral organoid Humans Mice neurodevelopment Neurogenesis organoid model Organoids - metabolism phospho-signaling phosphoproteome Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism proteome Proteome - metabolism Proteomics - methods Proto-Oncogene Proteins c-akt - metabolism Signal Transduction trans-omics transcriptome Transcriptome - genetics CP: Stem cell research neurodevelopment CP: Neuroscience transcriptome organoid model phospho-signaling trans-omics human cerebral organoid phosphoproteome proteome
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. [Display omitted] •A time-resolved trans-omic map of early human cerebral organoid (hCO) formation•Phospho-signaling converges on master regulators during hCO differentiation•Fidelity assessment of early hCOs in modeling embryonic brain development•Biochemical modulation of AKT signaling for early hCO differentiation Through comprehensive profiling of the phosphoproteome, proteome, and transcriptome, Chen et al. generate a time-resolved trans-omics map of early human cerebral organoid (hCO) formation. This resource reveals the multi-layered molecular controls involved in neural lineage acquisition and the convergence of phospho-signaling on master regulators during hCO differentiation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2024.114219