The Chen Lab
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Research

As one of the pioneers of the expansion microscopy technology, Dr. Fei Chen continues to utilize ExM in super resolution approaches. His lab is currently working on new tools for in situ transcriptomics and epigenomics.

 

Research

 
 

Spatial and Temporal Genomics

Cells in complex mammalian tissues, such as the brain, are spatially organized and dynamic, yet almost all genomic tools lack temporal and spatial resolution. Our laboratory, at the Broad institute, sets out to build a set of tools which will bridge single-cell genomics with space and time – to enable discoveries of where cell types are localized within intact tissues, when relevant transcriptional modules are active. To do this, we are developing novel technologies at the intersection of microscopy, genomics, synthetic biology, and computational analysis.  We are applying these tools to learn organizational principles governing development, and cellular mechanisms of disorganization during injury and disease. 

 

Spatial transcriptomics:

Current approaches for transcriptomic analysis involve grinding up or dissociating the tissue, while in situ hybridization (ISH) approaches are often limited to profiling one transcript at a time. However, to map the spatial heterogeneity of complex tissues requires us to bridge the divide between spatial and molecular resolution.  We are developing new tools at the intersection of microscopy and genomics. These include Slide-seq, an approach which enables high resolution profiling of the transcriptome using spatially barcoded bead arrays, as well highly multiplex microscopy methods. We are interested in using these approaches to understand tissue organization with respect to communication between cells and cellular networks in development and pathology.

Relevant Papers:

Stickels R.R.*, Murray M.*, Kumar P., Li J., Marshall J.L., Di Bella D., Arlotta P., Macosko E.Z.**, †, Chen F.**, † (Nature Biotechnology, 2020) Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2

Rodriques S.G.†, Stickels R.R.†, Goeva A., Martin C.A., Murray E., Vanderburg C.R., Welch J., Chen L.M., Chen F.*††, Macosko E.Z.*†† (Science, 2019) Slide-seq: A Scalable Technology for Measuring Genome-Wide Expression at High Spatial Resolution

Cleary B.*, Murray M., Alam S., Sinha A., Habibi E., Simonton S., Bezney J., Marshall J., Lander E.S.*, Chen F.*, Regev A.* (Bioarxiv 2019) Compressed sensing for imaging transcriptomics

 
The Chen lab - in situ epigenomics

Spatial genomics:

            The genome is 3 billion bases of DNA packaged into a 10-micron nucleus. The 3D organization of the genome, and the associated protein, RNAs, and cellular structures, regulate gene expression and cellular function. We are developing new genomic technologies which enable simultaneous sequencing and imaging of genomes in intact samples, uncovering genome-wide organizing principles across length scales in cells.

Relevant papers:

Payne A.C.*, Chiang Z.D.*, Reginato P.*, Mangiameli S.M., Murray E.M., Yao C., Church G.M., Boyden E.S.**, Buenrostro J.D.**, Chen F.** (In Press) 3-D genome sequencing in situ