RT Journal Article
SR Electronic
T1 Single cell epigenomic atlas of the developing human brain and organoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.30.891549
DO 10.1101/2019.12.30.891549
A1 Ryan S. Ziffra
A1 Chang N. Kim
A1 Amy Wilfert
A1 Maximilian Haeussler
A1 Alex M. Casella
A1 Pawel F. Przytycki
A1 Anat Kreimer
A1 Katherine S. Pollard
A1 Seth A. Ament
A1 Evan E. Eichler
A1 Nadav Ahituv
A1 Tomasz J. Nowakowski
YR 2019
UL http://biorxiv.org/content/early/2019/12/31/2019.12.30.891549.abstract
AB Dynamic changes in chromatin accessibility coincide with important aspects of neuronal differentiation, such as fate specification and arealization and confer cell type-specific associations to neurodevelopmental disorders. However, studies of the epigenomic landscape of the developing human brain have yet to be performed at single-cell resolution. Here, we profiled chromatin accessibility of >75,000 cells from eight distinct areas of developing human forebrain using single cell ATAC-seq (scATACseq). We identified thousands of loci that undergo extensive cell type-specific changes in accessibility during corticogenesis. Chromatin state profiling also reveals novel distinctions between neural progenitor cells from different cortical areas not seen in transcriptomic profiles and suggests a role for retinoic acid signaling in cortical arealization. Comparison of the cell type-specific chromatin landscape of cerebral organoids to primary developing cortex found that organoids establish broad cell type-specific enhancer accessibility patterns similar to the developing cortex, but lack many putative regulatory elements identified in homologous primary cell types. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.