Simulating psoriasis by altering transit amplifying cells.
Computational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (tau). Prolonging tau results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells and (4) a marked reduction in turnover time. The prolongation of tau is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency.
Grabe
Niels
N
Department of Medical Informatics, Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany. niels.grabe@med.uni-heidelberg.de
Neuber
Karsten
K
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
D018797:Cell Cycle Proteins