Our Research

Seeing is Believing

We’re working to develop tools to enable discovery-driven biology in tissues. We aim to comprehensively map molecular processes in healthy and diseased tissues.

Modern sequencing methods have brought many new insights into transcriptome-wide analysis, but crucially lose a native spatial context. Additionally, traditional fluorescent imaging methods only identify a few different molecules in one sample.

We developed seqFISH to identify tens of thousands of different molecules. We’re continually building on our ability to identify, quantify, and understand how cell environments drive cell function.

View our publications

Our Lab

The rapid growth of in situ imaging from a few genes to nearly the whole transcriptome was made possible by our interdisciplinary team of scientists and engineers. We developed the new molecular, fluidic, optical, and computational tools that made seqFISH+ possible.

2010

Cai Lab is founded
2012

First paper showing multiplexed RNA detection in single cells with super-resolution microscopy
2014

First demonstration of seqFISH
2016

249 genes imaged in brain sections with seqFISH
MEMOIR lineage tracing with seqFISH
Cai Lab moves from Caltech Chemistry to Caltech Biology
2017

10,212 genes identified in vitro with RNA SPOTs
2018

10,421 genes visualized by intron seqFISH
Cai Lab officially joins Caltech Biology
2019

10,000 mRNAs detected with RNA seqFISH+

Featured Collaborations

Elowitz Lab

Caltech

Biorxiv preprint (2020) Imaging cell lineage with a synthetic digital recording system

Nature Biotechnology (2019) In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription

Nature (2016) Synthetic recording and in situ readout of lineage information in single cells

Nature (2015) Combinatorial gene regulation by modulation of relative pulse timing

Molecular Cell (2014) Dynamic heterogeneity and DNA methylation in embryonic stem cells

Rothenberg Lab

Caltech

Cell Systems (2019) Single-Cell Analysis Reveals Regulatory Gene Expression Dynamics Leading to Lineage Commitment in Early T Cell Development

Anderson Lab

Caltech

Cell (2019) Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

Guttman Lab

Caltech

Cell (2018) Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

Yuan Lab

Harvard

Nature Biotechnology (2018) Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data

Genome Biology (2017) Challenges and emerging directions in single-cell analysis

Biorxiv preprint (2019) Giotto, a toolbox for integrative analysis and visualization of spatial expression data

Gradinaru Lab

Caltech

Cell (2014) Single-Cell Phenotyping within Transparent Intact Tissue through Whole-Body Clearing

Nature Protocols (2015) Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

Cairns Lab

University of Utah

Cell Research (2018) The adult human testis transcriptional cell atlas

Bronner Lab

Caltech

Nature Communications (2017) Identification of a neural crest stem cell niche by Spatial Genomic Analysis

Trapnell Lab

University of Washington

A Spatially resolved molecular Atlas of Human Endothelium (NIH)

Schier Lab

Harvard

Shendure Lab

University of Washington

Allen Discovery Center for Lineage Tracing