Liorni Niccolò, Napoli Alessandro, Castellana Stefano, Giallongo Sebastiano, Řeháková Daniela, Re Oriana Lo, Koutná Irena, Mazza Tommaso, Vinciguerra Manlio
Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza,71013, San Giovanni Rotondo, Italy.
International Clinical Research Center, St. Anne's University Hospital, 65691, Brno, Czech Republic.
Epigenomics. 2023 Sep;15(17):863-877. doi: 10.2217/epi-2023-0267. Epub 2023 Oct 17.
Human induced pluripotent stem cells (iPSCs) are inefficiently derived from somatic cells by overexpression of defined transcription factors. Overexpression of H2A histone variant macroH2A1.1, but not macroH2A1.2, leads to increased iPSC reprogramming by unclear mechanisms. Cleavage under targets and tagmentation (CUT&Tag) allows robust epigenomic profiling of a low cell number. We performed an integrative CUT&Tag-RNA-Seq analysis of macroH2A1-dependent orchestration of iPSCs reprogramming using human endothelial cells. We demonstrate wider genome occupancy, predicted transcription factors binding, and gene expression regulated by macroH2A1.1 during reprogramming, compared to macroH2A1.2. MacroH2A1.1, previously associated with neurodegenerative pathologies, specifically activated ectoderm/neural processes. CUT&Tag and RNA-Seq data integration is a powerful tool to investigate the epigenetic mechanisms occurring during cell reprogramming.
人类诱导多能干细胞（iPSC）是通过过表达特定转录因子从体细胞低效衍生而来的。H2A组蛋白变体macroH2A1.1而非macroH2A1.2的过表达，会通过不明机制导致iPSC重编程增加。靶向切割与标签化（CUT&Tag）技术能够对少量细胞进行强大的表观基因组分析。我们利用人内皮细胞对macroH2A1依赖的iPSC重编程调控进行了整合的CUT&Tag-RNA测序分析。我们证明，与macroH2A1.2相比，在重编程过程中macroH2A1.1具有更广泛的基因组占据、预测的转录因子结合以及基因表达调控。此前与神经退行性疾病相关的macroH2A1.1，特异性激活了外胚层/神经过程。CUT&Tag和RNA测序数据整合是研究细胞重编程过程中发生的表观遗传机制的有力工具。
