02616nas a2200361   4500000000100000008004100001260001200042100000900054700000900063700001100072700001000083700001000093700001000103700001100113700001000124700001100134700001100145700000900156700001200165700001000177700001100187700001100198700001000209700001000219700001000229700001200239245013000251856009900381300000900480490000700489520174400496022001402240       2023                            d  c07/20231 aMa S1 aMi Z1 aWang Z1 aSun L1 aLiu T1 aShi P1 aWang C1 aXue X1 aChen W1 aWang Z1 aYu Y1 aZhang Y1 aBao F1 aWang N1 aWang H1 aXia Q1 aLiu H1 aSun Y1 aZhang F00aSingle-cell sequencing analysis reveals development and differentiation trajectory of Schwann cells manipulated by M. leprae.  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011477&type=printable  a1-200 v173 a<p><strong>Background: </strong>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.</p>

<p><strong>Methodology/Principal Findings: </strong>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.</p>

<p><strong>Conclusion/Significance: </strong>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.</p>
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