Kearney Helen, Rak-Raszewska Aleksandra, Seijas-Gamardo Adrián, Escarda-Castro Enrique, Caiment Florian, Wieringa Paul, Moroni Lorenzo, Mota Carlos
MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands.
Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, 6229 ER, the Netherlands.
Stem Cell Rev Rep. 2025 Sep 18. doi: 10.1007/s12015-025-10971-z.
The field of human induced pluripotent stem cells (hiPSCs) has seen significant progress since the discovery of reprogramming somatic cells using the transcription factors Oct4, Sox2, Klf4, and c-Myc. hiPSCs are similar to embryonic stem cells in a primed state of pluripotency and have the potential to differentiate into any adult human cell type, offering a versatile tool for research and potential therapeutic applications. However, the efficiency of differentiation protocols for generating complex structures with multiple cell types, Like kidney organoids, remains a challenge. This study investigates the impact of treating hiPSCs with a low-dose dimethyl sulfoxide to enhance kidney organoid differentiation using the stepwise 2D monolayer-based protocol developed by Morizane et al. 2017. We found that treating hiPSCs with 1-2% DMSO affects gene expression of pluripotent transcription factors, the epigenetic landscape, and hiPSC colony morphology. Our findings also suggest DMSO treatment enhances the expression of the key metanephric mesenchyme nephron progenitor marker, SIX2 after 9 days of kidney organoid differentiation and helps improve hiPSC differentiation protocol efficiency toward the development of tubular kidney organoids. Further research is needed to fully elucidate the mechanisms underlying these effects and refine the differentiation process for potential in vitro research applications in biomedical research and drug development.
自利用转录因子Oct4、Sox2、Klf4和c-Myc对体细胞进行重编程的方法被发现以来，人类诱导多能干细胞（hiPSC）领域取得了显著进展。hiPSC在多能性的初始状态下与胚胎干细胞相似，有潜力分化为任何成人细胞类型，为研究和潜在治疗应用提供了一种多功能工具。然而，生成具有多种细胞类型的复杂结构（如肾类器官）的分化方案效率仍然是一个挑战。本研究使用Morizane等人在2017年开发的基于二维单层的逐步方案，研究了用低剂量二甲基亚砜处理hiPSC对增强肾类器官分化的影响。我们发现，用1-2%二甲基亚砜处理hiPSC会影响多能转录因子的基因表达、表观遗传格局和hiPSC集落形态。我们的研究结果还表明，在肾类器官分化9天后，二甲基亚砜处理可增强关键的后肾间充质肾单位祖细胞标志物SIX2的表达，并有助于提高hiPSC分化方案向管状肾类器官发育的效率。需要进一步研究以充分阐明这些效应背后的机制，并完善分化过程，以用于生物医学研究和药物开发中的潜在体外研究应用。
