Using human stem cells to understand & treat disease

PLURIPOTENT HUMAN CELLS

HUMAN GENETICS

GLIOBLASTOMA Josh Chenoweth, Paul Tesar & NIH facility

TERATOCARCINOMA

LIVER DEVELOPMENT & Jong-Hoon Kim (NIH & Korea University) FUNCTION Controlling differentiation in the mouse

A Mdm2 DAPI E3.5

Tr-

ICM

B E5.5 MEF mES mES mEpiSmEpiS mES

AlkIn AlkIn AlkIn JakIn

mES mEpiS hES

Mdm2 Trophectoderm

C E5.5 E5.5 epiblast embryo + 3 days in vitro

Epiblast

Mdm2 expression in the E3.5 (A) and E5.5 embryo (B). The E5.5 embryo prior to dissection of the epiblast Tesar et al., Nature, 2007 and the epiblast after 3 days in culture (C). Cell types in the early embryo Controlling human embryonic stem cells

Days Whole transcriptome characterization of undifferentiated hES cells after Zygote fertiliz ation

E2.5 Morula Mouse ES

E3.5

Trophectoderm

Human ES E4.5 Other labs Implant Epiblast Extra-emb. NIH E5.5

E6.5 Mes-endoderm Embryoid Body

Ectoderm Endoderm Controlling differentiation of human embryonic stem cells

Whole transcriptome characterization of hES cells

Human ES

Adult human tissue

Embryoid Bodies Controlling differentiation of human iPS cells

Whole transcriptome characterization of hES cells

ES iPS Parental cells Fibroblasts

iPS EBs

Adult human tissue

Embryoid Bodies Polymorphic levels of gene expression – Lung & prostate cancer

Glutathione S transferase (GSTT1)

ES iPS

BG03

ES06

GSTT1 Expression UC01 GSTT1 Copy Number

Agilent: CGH Analytics used to assess copy number Polymorphic levels of gene expression – Glioblastoma & Teratocarcinoma

MGMT +ve endothelial cells

–ve

Expression melanoma brain metastasis MGMT

MGMT

–ve & +ve breast cancer Expression MGMT +++ve lung cancer

Ingold B, Schraml P, Heppner FL Moch H, MGMT Promoter Methylation Homogeneous MGMT immunoreactivity correlates with unmethylated MGMT promoter status in brain metstases of various solid tumors PLoS One 2009 Generating Functional Hepatocytes

Human Hepatocytes HumanAlbumin

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