Chromatin accessibility dynamics in a model of human forebrain development
Citations Over TimeTop 1% of 2020 papers
Abstract
Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.
Related Papers
- → Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids(2021)350 cited
- → Patterning of brain organoids derived from human pluripotent stem cells(2022)39 cited
- → Deconstructing and reconstructing the human brain with regionally specified brain organoids(2020)34 cited
- → Review of Artificial Intelligence Applications and Algorithms for Brain Organoid Research(2020)22 cited
- → Development of Brain Organoids with Genome-Edited iPSC-Derived Brain Cells(2022)2 cited