Single-cell sequencing analysis reveals development and differentiation trajectory of Schwann cells manipulated by M. leprae.

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Shanshan Ma, Zihao Mi, Zhenzhen Wang, Lele Sun, Tingting Liu, Peidian Shi, Chuan Wang, Xiaotong Xue, Wenjie Chen, Zhe Wang, Yueqian Yu, Yuan Zhang, Fangfang Bao, Na Wang, Honglei Wang, Qianqian Xia, Hong Liu, Yonghu Sun, Furen Zhang
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2023
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0011477; https://doaj.org/article/778385527ec2477cb9271046ae35b289

Background M. leprae preferentially infects Schwann cells (SCs) in the peripheral nerves leading to nerve damage and irreversible disability. Knowledge of how M. leprae infects and interacts with host SCs is essential for understanding mechanisms of nerve damage and revealing potential new therapeutic strategies. Methodology/principal findings We performed a time-course single-cell sequencing analysis of SCs infected with M. leprae at different time points, further analyzed the heterogeneity of SCs, subpopulations associated with M. leprae infection, developmental trajectory of SCs and validated by Western blot or flow cytometry. Different subpopulations of SCs exhibiting distinct genetic features and functional enrichments were present. We observed two subpopulations associated with M. leprae infection, a stem cell-like cell subpopulation increased significantly at 24 h but declined by 72 h after M. leprae infection, and an adipocyte-like cell subpopulation, emerged at 72 h post-infection. The results were validated and confirmed that a stem cell-like cell subpopulation was in the early stage of differentiation and could differentiate into an adipocyte-like cell subpopulation. Conclusions/significance Our results present a systematic time-course analysis of SC heterogeneity after infection by M. leprae at single-cell resolution, provide valuable information to understand the critical biological processes underlying reprogramming and lipid metabolism during M. leprae infection of SCs, and increase understanding of the disease-causing mechanisms at play in leprosy patients as well as revealing potential new therapeutic strategies.