Fibroblasts, the most abundant cell type in the human body, play crucial roles in biological processes such as inflammation and cancer progression. They originate from the mesoderm or neural-crest-derived ectomesenchyme. Ectomesenchyme-derived fibroblasts contribute to facial formation and do not express HOX genes during development. The expression and role of the HOX genes in adult fibroblasts is not known. We investigated whether the developmental pattern persists into adulthood and under pathological conditions, such as cancer. We collected adult fibroblasts of ectomesenchymal and mesodermal origins from distinct body parts. The isolated fibroblasts were characterised by immunocytochemistry, and their transcriptome was analysed by whole genome profiling. Significant differences were observed between normal fibroblasts from the face (ectomesenchyme) and upper limb (mesoderm), particularly in genes associated with limb development, including HOX genes, e.g., HOXA9 and HOXD9. Notably, the pattern of HOX gene expression remained consistent postnatally, even in fibroblasts from pathological tissues, including inflammatory states and cancer-associated fibroblasts from primary and metastatic tumours. Therefore, the distinctive HOX gene expression pattern can serve as an indicator of the topological origin of fibroblasts. The influence of cell position and HOX gene expression in fibroblasts on disease progression warrants further investigation.

1st Faculty of Medicine and General University Hospital Department of Dermatovenereology Charles University Prague Czech Republic

1st Faculty of Medicine and The General University Hospital Department of Stomatology Charles University Prague Czech Republic

1st Faculty of Medicine Charles University BIOCEV Vestec Prague Czech Republic

1st Faculty of Medicine Institute of Anatomy Charles University Prague Czech Republic

1st Faculty of Medicine Institute of Biochemistry and Experimental Oncology Charles University Prague Czech Republic

3rd Faculty of Medicine Charles University Prague Burn Center Prague Czech Republic

Department for Biomedical Research East Slovak Institute of Cardiovascular Diseases Inc Košice Slovak Republic

Faculty of Chemical Technology Department of Informatics and Chemistry University of Chemistry and Technology Prague Prague Czech Republic

Faculty of Medicine Department of Pharmacology Pavol Jozef Šafárik University in Košice Košice Slovak Republic

Faculty of Pharmacy Department of Pharmacognosy and Botany Comenius University in Bratislava Bratislava Slovak Republic

Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic

School of Medicine Johns Hopkins University James Buchanan Brady Urological Institute Baltimore USA

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