Derivation and characteristics of induced pluripotent stem cells from a patient with acute myelitis

Shuo Cao; Xinyue Gao; Fangyuan Liu; Yanglin Chen; Qin Na; Qiaoqiao Meng; Peng Shao; Chen Chen; Yongli Song; Baojiang Wu; Xihe Li; Siqin Bao

doi:10.3389/fcell.2023.1172385

Derivation and characteristics of induced pluripotent stem cells from a patient with acute myelitis

Front Cell Dev Biol. 2023 Jul 14:11:1172385. doi: 10.3389/fcell.2023.1172385. eCollection 2023.

Authors

Shuo Cao^{1

2}, Xinyue Gao^{1

2}, Fangyuan Liu^{1

2}, Yanglin Chen^{1

2}, Qin Na^{1

2

3}, Qiaoqiao Meng^{1

2}, Peng Shao^{1

2}, Chen Chen^{1

2}, Yongli Song^{1

2}, Baojiang Wu^{1

2}, Xihe Li^{1

2

4}, Siqin Bao^{1

2}

Affiliations

¹ The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China.
² Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, China.
³ College of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.
⁴ Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot, China.

Abstract

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.

Keywords: acute myelitis; differentiation; ectoderm; induced pluripotent stem cells; reprogramming.

Grants and funding

This work was supported by grants National Key R&D Program of China (2022YFD1302202/3); Program of Higher-Level Talents of Inner Mongolia University (10000-21311201/058); Inner Mongolia Autonomous Region Natural Science Foundation (2021MS03003); Program of Advanced Foreign Experts Plan of Inner Mongolia Autonomous Region (21400-5213401).