Towards a transcriptional taxonomy of in vitro stem cell preparations

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• Franz-Josef Müller (University of Kiel / The Scripps Research Institute)
• Monday 07 September 2009, 16:00-17:00
• Cancer Research UK Cambridge Research Institute, Lecture Theatre.

If you have a question about this talk, please contact Laura Blackburn.

Human self-renewing multipotent and pluripotent stem cells that can be expanded in culture hold great promise for understanding and treating human disease. The commonly utilized characterization of stem cells in vitro with only a few stem cell markers and with some functional assays, like the teratoma assay, is underapprechiating the fact that there are important differences among seemingly “identical” stem cell preparations.

In order to better understand the molecular control of stem cell phenotypes, we performed comprehensive studies examining genome wide transcriptional profiles on a large and diverse set of samples of human neural, embryonic, induced pluripotent stem cells and pluripotent embryonal carcinoma cell lines.

This database – termed Stem Cell Matrix – allowed us to discover with a purely data driven approach clusters of diverse stem cell types based on global gene expression that distinguish human embryonic stem cell preparations from more restricted stem cell and progenitor populations.

We found for example, that pluripotent stem cells can be defined by means of an unique transcriptional phenotype in global gene expression data. This phenotype can also be discovered with other genome-wide profiling technologies, such as whole genome methylation and miRNA –profiling.

This algorithm could find its first application in identifying successfully reprogrammed induced pluripotent stem cell preparations without cumbersome and strenuous animal experimentation like it is required for the teratoma assay.

We used further bioinformatic analysis to uncover a protein–protein network (PluriNet) consisting of interacting proteins that is shared by the pluripotent cells. Analysis of published data showed that this protein interaction network appears to be a common characteristic of many types of pluripotent cells, including murine embryonic stem cells and induced pluripotent cells and human oocytes, is preserved across species boundaries and recapitulates many recent discoveries in ESC and iPSC research.

Our proof of principle study demonstrates that large-scale high throughput approaches such as whole genome transcriptional profiling are a valuable method to characterize and monitor stem cell preparations. This approach is analogous to taxonomical approaches that have been historically used to classify zoological specimens.

This talk is part of the CRI Seminars on Quantitative Biology series.

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