Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
Department of Animal Reproduction, Anatomy and Genomics, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059 Kraków, Poland.
Int J Mol Sci. 2022 Feb 10;23(4):1970. doi: 10.3390/ijms23041970.
The equine sarcoid is one of the most common neoplasias in the family. Despite the association of this tumor with the presence of bovine papillomavirus (BPV), the molecular mechanism of this lesion has not been fully understood. The transgenization of equine adult cutaneous fibroblast cells (ACFCs) was accomplished by nucleofection, followed by detection of molecular modifications using high-throughput NGS transcriptome sequencing. The results of the present study confirm that - and -mediated nucleofection strategy significantly affected the transcriptomic alterations, leading to sarcoid-like neoplastic transformation of equine ACFCs. Furthermore, the results of the current investigation might contribute to the creation of in vitro biomedical models suitable for estimating the fates of molecular dedifferentiability and the epigenomic reprogrammability of and transgenic equine ACFC-derived sarcoid-like cell nuclei in equine somatic cell-cloned embryos. Additionally, these in vitro models seem to be reliable for thoroughly recognizing molecular mechanisms that underlie not only oncogenic alterations in transcriptomic signatures, but also the etiopathogenesis of epidermal and dermal sarcoid-dependent neoplastic transformations in horses and other equids. For those reasons, the aforementioned transgenic models might be useful for devising clinical treatments in horses afflicted with sarcoid-related neoplasia of cutaneous and subcutaneous tissues.
马的肉瘤是家族中最常见的肿瘤之一。尽管这种肿瘤与牛乳头瘤病毒(BPV)的存在有关,但这种病变的分子机制尚未完全理解。通过核转染实现了马成年皮肤成纤维细胞(ACFC)的转基因化,然后使用高通量 NGS 转录组测序检测分子修饰。本研究的结果证实,- 和 - 介导的核转染策略显著影响了转录组的改变,导致马 ACFC 发生肉瘤样肿瘤转化。此外,目前的研究结果可能有助于创建体外生物医学模型,用于估计分子去分化和 及 转基因马 ACFC 衍生的肉瘤样细胞核的表观基因组重编程在马体细胞核克隆胚胎中的命运。此外,这些体外模型似乎可以可靠地全面认识分子机制,这些机制不仅是转录组特征中致癌改变的基础,也是马和其他马科动物表皮和真皮依赖肉瘤的肿瘤发生的病因。出于这些原因,上述转基因模型可能有助于为患有皮肤和皮下组织与肉瘤相关的肿瘤的马制定临床治疗方案。