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Advancing Models of Transcriptional Diversity in Human Brain Development

  • Author(s): Pebworth, Mark-Phillip L
  • Advisor(s): Alvarez-Buylla, Arturo
  • et al.
Abstract

The human cerebral cortex is comprised of a diverse set of neurons that are essential to its functions in perception, judgment, and sensory integration. The complexity of this organ emerges during development with the aid of tightly coordinated gene expression. Modern techniques now allow us to map the transcriptional diversity of cell types in the developing brain and the epigenetic alterations that generate them. Here, we explore two projects that advance our understanding of transcriptional diversity in the developing human cortex. The first maps cell-type-specific enhancers that might drive transcriptional diversity, and the second identifies subtypes of neuronal progenitors in the dorsal cortex. To map enhancers in part 1, we ran a PLAC-Seq, ATAC-seq, and RNA-seq on four FACS-sorted populations of human neural cell types and validated our cell-type specific results using a CRISPRi system. For part 2, the identification of neuronal progenitors relied on single cell RNA-seq results, paired with histology and viral labeling to identify 5 subpopulations. One of these populations stained for DLX5 and was related to a late neurogenic shift in neuronal progenitor location, while the other four populations dominated early neurogenesis through the germinal zone of the developing cortex. Interestingly, we did not see a clear relationship between morphology and cell type identity.

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