KCO Achievements, 2012-2017

Experimental and Computational Advancements in Single-Cell Biology

  • An early demonstration, in 18 cells, that revealed the potential for investigation and discovery at single-cell resolution
  • The first demonstration of a massively parallel single-cell sequencing method called Drop-Seq, in keeping with the KCO’s realization that biological discoveries would require profiling massive numbers of single cells
  • Invented innovative new methods to study, sequence and profile single nuclei (sNuc-seq, Div-Seq, and DroNc-seq, the first massively parallel single-nucleus RNA-seq)
  • Developed Perturb-Seq, the first method for pooled CRISPR screens with scRNA-seq readout
  • Developed computational tools to accompany new technologies, such as algorithms to discover cell types, their positions in tissue, their continuous states, temporal transitions, and functional interactions, and the molecular regulatory networks that govern them
  • Applied new experimental and computational tools to patient samples, including pioneering the first single-cell analyses of cancer

Flagship projects

  • Th17 cells – defined the regulatory circuits controlling the balance between healthy and pathogenic Th17 cells
  • Retina – developed the single-cell RNA sequencing method Drop-Seq and used it to identify all the types of neurons in the retina, including previously unknown cell types
  • Tumor ecosystems – pioneered the single-cell analysis of tumors and their environment, including immune cells
  • Gut – developed a cell atlas of the small intestine, identifying new types of sensory cells

Collaborative projects

  • Identified the role of core circadian clock genes in regulating leukemia stem cells (with Ben Ebert lab)
  • Developed sNuc-Seq and Div-Seq to perform single-cell profiling in the adult brain and some tumors (with Feng Zhang lab)
  • Invented method for single-nucleosome analysis of combinatorial histone modifications in cancer (Bradley Bernstein lab)

Leveraged projects

  • Analyzed additional tumor ecosystems, including glioma, synovial sarcoma, and head and neck squamous cell carcinoma (with Mario Suva, Bradley Berstein, and Nicolo Riggi labs)
  • Characterized the lung epithelium in health and allergy (with Vijay Kuchroo lab)