Novel Potential Markers of Myofibroblast Differentiation Revealed by Single-Cell RNA Sequencing Analysis of Mesenchymal Stromal Cells in Profibrotic and Adipogenic Conditions

Grigorieva, O.; Basalova, N.; Vigovskiy, M.; Arbatskiy, M.; Dyachkova, U.; Kulebyakina, M.; Kulebyakin, K.; Tyurin-Kuzmin, P.; Kalinina, N.; Efimenko, A.

Авторы: Grigorieva Olga, Basalova Nataliya, Vigovskiy Maksim, Arbatskiy Mikhail, Dyachkova Uliana, Kulebyakina Maria, Kulebyakin Konstantin, Tyurin-Kuzmin Pyotr, Kalinina Natalia, Efimenko Anastasia
Журнал: BIOMEDICINES
Том: 11
Номер: 3
Год издания: 2023
Номер статьи: 840
DOI: 10.3390/biomedicines11030840
Аннотация: Mesenchymal stromal cells (MSCs) are the key regulators of tissue homeostasis and repairafter damage. Accumulating evidence indicates the dual contribution of MSCs into the developmentof fibrosis induced by chronic injury: these cells can suppress the fibrotic process due to paracrineactivity, but their promoting role in fibrosis by differentiating into myofibroblasts has also beendemonstrated. Many model systems reproducing fibrosis have shown the ability of peroxisomeproliferator-activated receptor (PPAR) agonists to reverse myofibroblast differentiation. Thus, thedifferentiation of multipotent cells into myofibroblasts and adipocytes can be considered as processes that require the activation of opposite patterns of gene expression. To test this hypothesis, we analyzed single cell RNA-Seq transcriptome of human adipose tissue MSCs after stimulation of the myofibroblast or adipogenic differentiation and revealed several genes that changed their expression in a reciprocal manner upon these conditions. We validated the expression of selected genes by RT-PCR, and evaluated the upregulation of several relevant proteins using immunocytochemistry, refining the results obtained by RNA-Seq analysis. We have shown, for the first time, the expression of neurotrimin (NTM), previously studied mainly in the nervous tissue, in human adipose tissue MSCs, and demonstrated its increased gene expression and clustering of membrane receptors upon the stimulation of myofibroblast differentiation. We also showed an increased level of CHD3 (Chromodomain-Helicase-DNA-binding protein 3) in MSCs under profibrotic conditions, while retinol dehydrogenase-10 (RDH10) was detected only in MSCs after adipogenic induction, which contradicted the data of transcriptomic analysis and again highlights the need to validate the data obtained by omics methods. Our findings suggest the further analysis of the potential contribution of neurotrimin and CHD3 in the regulation of myofibroblast differentiation and the development of fibrosis
Добавил в систему: Арбатский Михаил Спартакович

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Novel Potential Markers of Myofibroblast Differentiation Revealed by Single-Cell RNA Sequencing Analysis of Mesenchymal Stromal Cells in Profibrotic and Adipogenic Conditionsстатья Электронная публикация