Cao Shuo, Gao Xinyue, Liu Fangyuan, Chen Yanglin, Na Qin, Meng Qiaoqiao, Shao Peng, Chen Chen, Song Yongli, Wu Baojiang, Li Xihe, Bao Siqin
The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China.
Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, China.
Front Cell Dev Biol. 2023 Jul 14;11:1172385. doi: 10.3389/fcell.2023.1172385. eCollection 2023.
The emergence and development of induced pluripotent stem cells (iPSCs) provides an approach to understand the regulatory mechanisms of cell pluripotency and demonstrates the great potential of iPSCs in disease modeling. Acute myelitis defines a group of inflammatory diseases that cause acute nerve damage in the spinal cord; however, its pathophysiology remains to be elusive. In this study, we derived skin fibroblasts from a patient with acute myelitis (P-HAF) and then reprogrammed P-HAF cells to iPSCs using eight exogenous factors (namely, and ). We performed transcriptomic analysis of the P-HAF and compared the biological characteristics of the iPSCs derived from the patient (P-iPSCs) with those derived from normal individuals in terms of pluripotency, transcriptomic characteristics, and differentiation ability toward the ectoderm. Compared to the control iPSCs, the P-iPSCs displayed similar features of pluripotency and comparable capability of ectoderm differentiation in the specified culture. However, when tested in the common medium, the P-iPSCs showed attenuated potential for ectoderm differentiation. The transcriptomic analysis revealed that pathways enriched in P-iPSCs included those involved in Wnt signaling. To this end, we treated iPSCs and P-iPSCs with the Wnt signaling pathway inhibitor IWR1 during the differentiation process and found that the expression of the ectoderm marker was increased significantly in P-iPSCs. This study provides a novel approach to investigating the pathogenesis of acute myelitis.
诱导多能干细胞(iPSCs)的出现和发展为理解细胞多能性的调控机制提供了一种方法,并展示了iPSCs在疾病建模中的巨大潜力。急性脊髓炎定义了一组导致脊髓急性神经损伤的炎症性疾病;然而,其病理生理学仍不清楚。在本研究中,我们从一名急性脊髓炎患者身上获取皮肤成纤维细胞(P-HAF),然后使用八个外源性因子(即 和 )将P-HAF细胞重编程为iPSCs。我们对P-HAF进行了转录组分析,并在多能性、转录组特征以及向外胚层的分化能力方面,将患者来源的iPSCs(P-iPSCs)与正常个体来源的iPSCs的生物学特性进行了比较。与对照iPSCs相比,P-iPSCs在特定培养条件下表现出相似的多能性特征和相当的外胚层分化能力。然而,在普通培养基中进行测试时,P-iPSCs的外胚层分化潜力减弱。转录组分析显示,P-iPSCs中富集的通路包括那些参与Wnt信号传导的通路。为此,我们在分化过程中用Wnt信号通路抑制剂IWR1处理iPSCs和P-iPSCs,发现P-iPSCs中外胚层标志物 的表达显著增加。本研究为研究急性脊髓炎的发病机制提供了一种新方法。