seqFISH is a key technology for mapping gene expression and generating the Human Cell Atlas (HCA)

 
 

HCA is the successor to the Human Genome Project.  All the cells in our body have the same genome but different mRNA gene expression profiles.  For example, neurons will have a different set of genes expressed than skin cells.  seqFISH can profile the transcriptome of different cell types directly in their tissue context.  This will allow us to generate a spatial map of cell types and states directly in tissues with single molecule accuracy and without the perturbative effects of dissociation.

 

 

Why Spatial information?

Tissues are composed of a heterogeneous population of cells. It is not just the brain that is complex, even a tissue we think of as simple, such as the skin, is composed of different cell types, including differentiated cells, progenitors, stem cells, and immune cells.  To understand the ecology and micro-environment of tissues, we have to map the spatial organization of cell types and their interactions at the single cell level.  

 

Spatial organization of cells in the hippocampus.

 
 

Why Single cells?

Averaging populations of cells obscures individual properties that may be critical to understanding cell type, function, or even disease state. For example, a single sub-population of cells often malfunctions in a disease.  We need to pinpoint that sub-population of cells and determine how they signal with their neighbors in order to better understand and ultimately treat the disease. Relying on average cell properties or on genome sequence alone (which is the same for all cells) can yield misleading results.