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

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

Elisabet Andersson, Alistair Chalk

hES colony stained for Nanog and SSEA-1

What is a stem cell and why are bioinformaticsimportant tools in studying stem cells and differentiation?

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

Elisabet Andersson, Alistair Chalk

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Factors such as Nanog, Oct4, Sox2, Klf4, Lin28 are introduced into eg fibroblast and cells are screened for totipotency

The Stem Cell

-

maker of all other cells

Embryonic Stem cell

Specific set of markers eg:

Mouse: Nanog, Oct4,

SSEA1, Tra-1-80human: Nanog, Oct4,

SSEA4, Tra-1-60

Characteristics:totipotentin definitive growth

differentiation

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

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

Elisabet Andersson, Alistair Chalk

Multipotent stem cells:

Hematopoietic stem cells

Neuronal stem cells

Hepatic stem cells

Muscle stem cells

etc1

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Intracellular changes during differentiation

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……

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

Elisabet Andersson, Alistair Chalk

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

Spatial aspects = many data points = huge data sets

Anterior – posterior

Dorsal – ventral

Anterior

Posterior

Ventral Dorsal

Spinalcord

midbrain

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

Elisabet Andersson, Alistair Chalk

medium

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

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 ChalkY

eo, G

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t al

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Molecular regulation of stem cells Differentiation Studies

Gene expression profile

microRNA profile

Promoter regulation

Epigenetic changes

Post-translational

Phosphorylations

Exon usage

etc

Massive data generated at many different levels How can this be integrated?

Ensembl

ArrayExpress

ArrayExpressAtlas

DAVIDPathwayCommons

CellDesignerChip-Chip analysis using Ringo

Chipster

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

Elisabet Andersson, Alistair Chalk

Dry lab rats(ie bioinformatics)

Wet lab Rats(ie biologists)

Experimentaldesign

Micro array Deep sequencing

microRNAs

PhylogenyStructural relations

System biology

Chip-on-ChipChip-IP

Domain identification

Drug discovery

Analysis of existing

databases

Data handing

Promoter/enhancersgenome wide

Predicitions

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

Elisabet Andersson, Alistair Chalk