Table6_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）的涌现与发展，为解析细胞多能性的调控机制提供了途径，并彰显了iPSCs在疾病模型构建中的巨大潜力。急性髓炎界定了一类导致脊髓急性神经损伤的炎症性疾病；然而，其病理生理学仍显扑朔迷离。在本研究中，我们从一位急性髓炎患者（P-HAF）中提取皮肤成纤维细胞，并利用八种外源性因子（即，OCT4、SOX2、c-MYC、KLF4、NANOG、LIN28、RARG和LRH1）将该P-HAF细胞重编程为iPSCs。我们对P-HAF进行了转录组分析，并从多能性、转录组特征和向表皮分化能力等方面，将患者来源的iPSCs（P-iPSCs）与来自正常个体的iPSCs的生物特性进行了比较。与对照iPSCs相比，P-iPSCs在特定培养条件下显示出相似的多能性特征和相等的表皮分化能力。然而，在常规培养基中测试时，P-iPSCs的表皮分化潜力有所减弱。转录组分析揭示了P-iPSCs中富集的通路包括参与Wnt信号传导的通路。鉴于此，我们在分化过程中对iPSCs和P-iPSCs进行了Wnt信号传导通路抑制剂IWR1的处理，并发现P-iPSCs中表皮标记物Sox1的表达显著增加。本研究为急性髓炎发病机制的探究提供了一种新颖的方法。