Predictive Biology
Genetically Diverse Stem Cell Panels
We use a proprietary panel of mouse ES and derivative lines for most genetic screens. We use human induced pluripotent stem cell lines for validation of modifier genes and mechanisms discovered in genetic screens. We also use primary cells and tissues when appropriate.
For our main genetic screening resource we produced over 1,000 ES cell lines from DO mice. The ES lines are densely genotyped and individualized genomes and transcriptomes are constructed for each cell line.
Lineage Restricted Stem Cell Banks. Pluripotent stem cell lines provide access to almost any cell type, in principle. In this way, our cell lines are an extremely versatile, permanent and reusable resources. We are establishing lineage restricted stem cell banks by differentiation, which are themselves also permanent renewable resources for screening. These cells can be be further differentiated to terminally differentiated cell types.
We have conducted genetic screens for compound/drug response genes using panels of 200-300 cell lines. These homogeneous cell models include:
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ES Cells
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Neural Progenitor Cells
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Astrocytes
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Cardiomyocytes
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many other cell types
Haplotype reconstruction of a typical DO genome.
Organoids. Organoids are three-dimensional, self-organizing, stem-cell-derived structures that resemble their in vivo tissue counterparts (Lancaster and Knoblich, Science. 2014;345:1247125). We conduct studies with organoid models because of their tissue-like organization, cell interaction, and more authentic cell types. For analysis, we use single cell technologies such as single cell RNAseq, high content analysis imaging and FACS to manage the presence of multiple cell types within an organoid. Most of our organoid studies have been with mouse or human cerebral organoids. We have also produced intestinal, retinal and otological organoids.
