Table7_Derivation and characteristics of induced pluripotent stem cells from a patient with acute myelitis.XLS

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, OCT4, SOX2, c-MYC, KLF4, NANOG, LIN28, RARG, and LRH1). 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 Sox1 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）的涌现与进展，为解析细胞多能性的调控机制提供了一种途径，并彰显了iPSCs在疾病建模方面的巨大潜力。急性脊髓炎界定了一组引起脊髓急性神经损伤的炎症性疾病，然而，其病理生理学仍扑朔迷离。在本研究中，我们从一位急性脊髓炎患者（P-HAF）中分离出皮肤成纤维细胞，并利用八种外源性因子（即OCT4、SOX2、c-MYC、KLF4、NANOG、LIN28、RARG和LRH1）将P-HAF细胞重编程为iPSCs。我们对P-HAF进行了转录组分析，并从生物学特性上对比了患者来源的iPSCs（P-iPSCs）与正常个体来源的iPSCs在多能性、转录组特征以及向外胚层分化的能力。与对照iPSCs相比，P-iPSCs在外胚层分化的指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，在常规培养基中测试时，P-iPSCs的外胚层分化潜力有所减弱。转录组分析揭示了P-iPSCs中富集的通路包括涉及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中外胚层标记物Sox1的表达显著增加。本研究为探究急性脊髓炎的发病机制提供了一种新颖的方法。