Inferring and perturbing cell fate regulomes in human brain organoids

Combined with single-cell genomic technologies provide opportunities to examine gene regulatory networks underlying human brain development. Here we acquire single-cell transcriptome and accessible chromatin data over a dense time course in human organoids covering neuroepithelial formation, patterning, brain regionalization and neurogenesis, and identify temporally dynamic and brain-region-specific regulatory regions. We developed Pando-a flexible framework that incorporates multi-omic data and predictions of transcription-factor-binding sites to infer a global gene regulatory network describing organoid development. We use pooled genetic perturbation with single-cell transcriptome readout to assess…

• NS
  National Science Foundation
• SV
  Silicon Valley Community Foundation

  Award: CZF2019-002440
• CH
  Children’s Hospital of Wisconsin Research Institute
• MC
  Murdoch Children's Research Institute
• BI
  Boehringer Ingelheim Fonds
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• MU
  Murdoch University
• ET
  Eidgenössische Technische Hochschule Zürich
• NC
  National Center of Competence in Research Chemical Biology
• R
  RIKEN