Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human keratinocytes after stimulation with recombinant human cytokines to study the events controlling cell migration)

ABSTRACT: Cellular decisions leading to a sustained cellular migration constitute a critical parameter during wound healing and metastasis. Cellular decision processes for migration involve signaling pathways as well as gene expression regulation that have been not yet studied in an integrated way. Here, heterologous cocultures combining primary human keratinocytes and genetically defined murine fibroblasts served as a model for wound healing of human skin to gain a systemic view of the underlying principles of cellular decision making towards migration. By inverse modeling of time series of gene expression data followed by experimental validation we show that (I) pulse-like activation of the proto-oncogene receptor Met by its ligand HGF triggers a responsive system state, (II) permanent, time sequential activation of the EGF-receptor is required to initiate and sustain migration, and (III), context information for enhancing, delaying or stopping migration is provided via the activity of the PKA-signaling pathway. Our study reveals a complex orchestration of events controlling cell migration.

ORGANISM(S): Homo sapiens

SUBMITTER: Chris and Axel Lawerenz and Szabowski 

PROVIDER: E-TABM-440 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene network dynamics controlling keratinocyte migration.

Busch Hauke H   Camacho-Trullio David D   Rogon Zbigniew Z   Breuhahn Kai K   Angel Peter P   Eils Roland R   Szabowski Axel A  

Molecular systems biology 20080701

Translation of large-scale data into a coherent model that allows one to simulate, predict and control cellular behavior is far from being resolved. Assuming that long-term cellular behavior is reflected in the gene expression kinetics, we infer a dynamic gene regulatory network from time-series measurements of DNA microarray data of hepatocyte growth factor-induced migration of primary human keratinocytes. Transferring the obtained interactions to the level of signaling pathways, we predict in  ...[more]