Cell-type-specific 3D epigenomes in the developing human cortex

Cell-type-specific 3D epigenomes in the developing human cortex. Song, M., Pebworth, M., Yang, X., Abnousi, A., Fan, C., Wen, J., Rosen, J. D, Choudhary, M. N K, Cui, X., Jones, I. R, Bergenholtz, S., Eze, U. C, Juric, I., Li, B., Maliskova, L., Lee, J., Liu, W., Pollen, A. A, Li, Y., Wang, T., Hu, M., Kriegstein, A. R, & Shen, Y. Nature, 587(7835):644–649, October, 2020.
abstract bibtex

Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone(1,2). Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.

@ARTICLE{Song2020-fz,
  title    = "Cell-type-specific {3D} epigenomes in the developing human cortex",
  author   = "Song, Michael and Pebworth, Mark-Phillip and Yang, Xiaoyu and
              Abnousi, Armen and Fan, Changxu and Wen, Jia and Rosen, Jonathan
              D and Choudhary, Mayank N K and Cui, Xiekui and Jones, Ian R and
              Bergenholtz, Seth and Eze, Ugomma C and Juric, Ivan and Li,
              Bingkun and Maliskova, Lenka and Lee, Jerry and Liu, Weifang and
              Pollen, Alex A and Li, Yun and Wang, Ting and Hu, Ming and
              Kriegstein, Arnold R and Shen, Yin",
  abstract = "Lineage-specific epigenomic changes during human corticogenesis
              have been difficult to study owing to challenges with sample
              availability and tissue heterogeneity. For example, previous
              studies using single-cell RNA sequencing identified at least 9
              major cell types and up to 26 distinct subtypes in the dorsal
              cortex alone(1,2). Here we characterize cell-type-specific
              cis-regulatory chromatin interactions, open chromatin peaks, and
              transcriptomes for radial glia, intermediate progenitor cells,
              excitatory neurons, and interneurons isolated from
              mid-gestational samples of the human cortex. We show that
              chromatin interactions underlie several aspects of gene
              regulation, with transposable elements and disease-associated
              variants enriched at distal interacting regions in a
              cell-type-specific manner. In addition, promoters with increased
              levels of chromatin interactivity-termed super-interactive
              promoters-are enriched for lineage-specific genes, suggesting
              that interactions at these loci contribute to the fine-tuning of
              transcription. Finally, we develop CRISPRview, a technique that
              integrates immunostaining, CRISPR interference, RNAscope, and
              image analysis to validate cell-type-specific cis-regulatory
              elements in heterogeneous populations of primary cells. Our
              findings provide insights into cell-type-specific gene expression
              patterns in the developing human cortex and advance our
              understanding of gene regulation and lineage specification during
              this crucial developmental window.",
  journal  = "Nature",
  volume   =  587,
  number   =  7835,
  pages    = "644--649",
  month    =  oct,
  year     =  2020,
  language = "en"
}

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