Single-Cell ATAC-seq of the Developing Human Brain

nemo:std-y936g22 · Short name: kriegstein_sc_ATACseq_proj

biccn ['cell nucleus']

Project at a glance

Program
biccn
Submission status
['cell nucleus']
Funding support
Not listed
Consortium RRID
Not listed
Organizations
University of California, San Francisco

Scope

Taxa
No taxa listed
Modalities
epigenome
Techniques
atac-seq
Assays
No assays listed
License
CC BY 4.0

Description

"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."

Funding & grants

No grant information listed for this project.

Contact & contributors

Contributors

  • Arnold Kriegstein University of California, San Francisco 0000-0001-5742-2990
  • Tomasz Nowakowski University of California, San Francisco 0000-0003-2345-4964
  • Ryan Ziffra University of California, San Francisco
  • Li Wang University of California, San Francisco

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Publications in this project

Project attributes

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Documentation & resources