Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems
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Date
2024-07
Publication Type
Journal Article
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yes
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Abstract
Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.
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Publication status
published
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Editor
Book title
Journal / series
Volume
27 (7)
Pages / Article No.
1376 - 1386
Publisher
Nature
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Cell fate and cell lineage; Developmental neurogenesis; Epigenetics; Epigenomics
Organisational unit
09485 - Treutlein, Barbara / Treutlein, Barbara
Notes
Funding
758877 - Reconstructing human cortex development and malformation with single-cell transcriptomics (EC)
874606 - Molecular atlas of the brain across the human lifespan (EC)
192604 - Resolving and controlling brain patterning in human cerebral organoids (SNF)
874606 - Molecular atlas of the brain across the human lifespan (EC)
192604 - Resolving and controlling brain patterning in human cerebral organoids (SNF)
Related publications and datasets
Is source of: http://hdl.handle.net/20.500.11850/681680