Pfeiferová Lucie, Španko Michal, Šáchová Jana, Hradilová Miluše, Pienta Kenneth J, Valach Jaroslav, Machoň Vladimír, Výmolová Barbora, Šedo Aleksi, Bušek Petr, Szabo Pavol, Lacina Lukáš, Gál Peter, Kolář Michal, Smetana Karel
Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
Faculty of Chemical Technology, Department of Informatics and Chemistry, University of Chemistry and Technology in Prague, Prague, Czech Republic.
Histochem Cell Biol. 2025 Mar 10;163(1):38. doi: 10.1007/s00418-025-02362-9.
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.
成纤维细胞是人体中最丰富的细胞类型，在炎症和癌症进展等生物学过程中发挥着关键作用。它们起源于中胚层或神经嵴衍生的外胚间充质。外胚间充质来源的成纤维细胞有助于面部形成，并且在发育过程中不表达HOX基因。HOX基因在成年成纤维细胞中的表达和作用尚不清楚。我们研究了这种发育模式是否会持续到成年期以及在癌症等病理条件下是否依然存在。我们从不同身体部位收集了外胚间充质和中胚层来源的成年成纤维细胞。通过免疫细胞化学对分离出的成纤维细胞进行表征，并通过全基因组分析对其转录组进行分析。观察到来自面部（外胚间充质）和上肢（中胚层）的正常成纤维细胞之间存在显著差异，特别是在与肢体发育相关的基因方面，包括HOX基因，如HOXA9和HOXD9。值得注意的是，即使在来自病理组织的成纤维细胞中，包括炎症状态以及原发性和转移性肿瘤的癌症相关成纤维细胞中，HOX基因的表达模式在出生后仍保持一致。因此，独特的HOX基因表达模式可作为成纤维细胞拓扑起源的指标。成纤维细胞中细胞位置和HOX基因表达对疾病进展的影响值得进一步研究。
