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Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet, 18-24 September 2008

Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet, 18-24 September 2008 Elisabet Andersson, Alistair Chalk. Stem Cell Biology and Bioinformatic Tools DBRM, Karolinska Institutet 18-24 September 2008 Elisabet Andersson, Alistair Chalk.

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Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet, 18-24 September 2008

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  1. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Stem Cell Biology and Bioinformatic Tools DBRM, Karolinska Institutet 18-24 September 2008 Elisabet Andersson, Alistair Chalk

  2. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk What is a stem cell and why are bioinformatics important tools in studying stem cells and differentiation? hES colony stained for Nanog and SSEA-1

  3. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk The Stem Cell - maker of all other cells Byrne, J. A. Hum. Mol. Genet. 2008 17:R37-41R; doi:10.1093/hmg/ddn053 Factors such as Nanog, Oct4, Sox2, Klf4, Lin28 are introduced into eg fibroblast and cells are screened for totipotency

  4. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Embryonic Stem cell Loss of stem cell markers eg Nanog and Oct4 Induction of more lineage specific markers eg: Ectoderm progenitors: Sox2 Mesoderm progenitors: Brachyury T Endoderm progenitors: Sox17 differentiation Specific set of markers eg: Mouse: Nanog, Oct4, SSEA1, Tra-1-80 human: Nanog, Oct4, SSEA4, Tra-1-60 Characteristics: totipotent in definitive growth Multipotent stem cells: Hematopoietic stem cells Neuronal stem cells Hepatic stem cells Muscle stem cells etc1

  5. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Intracellular changes during differentiation Chen, L. et al. Hum. Mol. Genet. 2008 17:R23-27R; doi:10.1093/hmg/ddn050

  6. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Huge data sets are rapidly generated via variety of experimental designs that most stem cell biologists are set out to delineate……

  7. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Yeo, G. W. et al. Hum. Mol. Genet. 2008 17:R67-75R; doi:10.1093/hmg/ddn065 What goes on when a stem cell go from A to B to C etc? Temporal aspects = many data points = huge data sets Stem cell – multipotent progentitor – bipotent progenitor – mature cell

  8. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Spatial aspects = many data points = huge data sets Anterior – posterior Dorsal – ventral

  9. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk • Other factors influencing: • addition/removal of factors eg Shh, Fgf8, Fgf2, Egf • addition/removal of different medium supplements eg N2, B27 • manufacturer • culture conditions • passage of cells medium

  10. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Differentiation Studies Molecular regulation of stem cells Gene expression profile microRNA profile Promoter regulation Epigenetic changes Post-translational Phosphorylations Exon usage etc Yeo, G. W. et al. Hum. Mol. Genet. 2008 17:R67-75R; doi:10.1093/hmg/ddn065 Massive data generated at many different levels How can this be integrated?

  11. Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Ensembl ArrayExpress ArrayExpressAtlas Chipster DAVID PathwayCommons Chip-Chip analysis using Ringo CellDesigner

  12. Predicitions Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet,18-24 September 2008 Elisabet Andersson, Alistair Chalk Experimental design Micro array Deep sequencing Drug discovery microRNAs Wet lab Rats (ie biologists) Phylogeny Structural relations Promoter/enhancers genome wide Dry lab rats (ie bioinformatics) Analysis of existing databases Domain identification Chip-on-Chip Chip-IP Data handing System biology

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