Stem Cell Biology and Bioinformatic Tools, DBRM, Karolinska Institutet, 18-24 September 2008
description
Transcript of 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
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
Byrn
e, J. A. H
um
. Mo
l. Gen
et. 2008 17:R37-
41R; d
oi:10.1093/h
mg
/dd
n053
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
Ch
en, L
. et
al. H
um
. Mo
l. G
enet
. 200
8 17
:R23
-27R
; d
oi:
10.1
093/
hm
g/d
dn
050
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
Yeo
, G. W
. et
al. H
um
. Mo
l. G
enet
. 200
8 17
:R67
-75R
; d
oi:
10.1
093/
hm
g/d
dn
065
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
. W. e
t al
. Hu
m. M
ol.
Gen
et. 2
008
17:R
67-7
5R;
do
i:10
.109
3/h
mg
/dd
n06
5
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