Show simple item record

dc.contributor.authorZiffra, Ryan S
dc.contributor.authorKim, Chang N
dc.contributor.authorRoss, Jayden M
dc.contributor.authorWilfert, Amy
dc.contributor.authorTurner, Tychele N
dc.contributor.authorHaeussler, Maximilian
dc.contributor.authorCasella, Alex M
dc.contributor.authorPrzytycki, Pawel F
dc.contributor.authorKeough, Kathleen C
dc.contributor.authorShin, David
dc.contributor.authorBogdanoff, Derek
dc.contributor.authorKreimer, Anat
dc.contributor.authorPollard, Katherine S
dc.contributor.authorAment, Seth A
dc.contributor.authorEichler, Evan E
dc.contributor.authorAhituv, Nadav
dc.contributor.authorNowakowski, Tomasz J
dc.date.accessioned2021-10-19T19:08:01Z
dc.date.available2021-10-19T19:08:01Z
dc.date.issued2021-10-06
dc.identifier.urihttp://hdl.handle.net/10713/16882
dc.description.abstractDuring mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscape1. In the developing brain, cell fate specification and topographic identity are important for defining cell identity2 and confer selective vulnerabilities to neurodevelopmental disorders3. Here, to identify cell-type-specific chromatin accessibility patterns in the developing human brain, we used a single-cell assay for transposase accessibility by sequencing (scATAC-seq) in primary tissue samples from the human forebrain. We applied unbiased analyses to identify genomic loci that undergo extensive cell-type- and brain-region-specific changes in accessibility during neurogenesis, and an integrative analysis to predict cell-type-specific candidate regulatory elements. We found that cerebral organoids recapitulate most putative cell-type-specific enhancer accessibility patterns but lack many cell-type-specific open chromatin regions that are found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed unexpected diversity among neural progenitor cells in the cerebral cortex and implicated retinoic acid signalling in the specification of neuronal lineage identity in the prefrontal cortex. 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.en_US
dc.description.urihttps://doi.org/10.1038/s41586-021-03209-8en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofNatureen_US
dc.rights© 2021. The Author(s).en_US
dc.subjectcell fate specificationen_US
dc.subjectcell type diversityen_US
dc.subject.meshChromatinen_US
dc.subject.meshEpigenomicsen_US
dc.titleSingle-cell epigenomics reveals mechanisms of human cortical development.en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41586-021-03209-8
dc.identifier.pmid34616060
dc.source.journaltitleNature
dc.source.volume598
dc.source.issue7879
dc.source.beginpage205
dc.source.endpage213
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland


This item appears in the following Collection(s)

Show simple item record