Reconstructing protein networks of epithelial differentiation from histological sections.
BACKGROUND
For systems biology of complex stratified epithelia like human epidermis, it will be of particular importance to reconstruct the spatiotemporal gene and protein networks regulating keratinocyte differentiation and homeostasis.


RESULTS
Inside the epidermis, the differentiation state of individual keratinocytes is correlated with their respective distance from the connective tissue. We here present a novel method to profile this correlation for multiple epithelial protein biomarkers in the form of quantitative spatial profiles. Profiles were computed by applying image processing algorithms to histological sections stained with tri-color indirect immunofluorescence. From the quantitative spatial profiles, reflecting the spatiotemporal changes of protein expression during cellular differentiation, graphs of protein networks were reconstructed.


CONCLUSIONS
Spatiotemporal networks can be used as a means for comparing and interpreting quantitative spatial protein expression profiles obtained from different tissue samples. In combination with automated microscopes, our new method supports the large-scale systems biological analysis of stratified epithelial tissues.
Hamamatsu Tissue Imaging and Analysis (TIGA) Center, BIOQUANT, University Heidelberg, Heidelberg, Germany. niels.grabe@med.uni-heidelberg.de
Niels
N
Grabe
Thora
T
Pommerencke
Thorsten
T
Steinberg
Hartmut
H
Dickhaus
Pascal
P
Tomakidi
D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D015603:Keratinocytes / Q000145:classification* / Q000166:cytology / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D046888:Tissue Array Analysis / Q000379:methods*; D014018:Tissue Distribution
D020543:Proteome