Abstract

Myoblasts could transdifferentiate into adipocytes or adipocyte-like cells, which have the capability of producing and storing intracellular lipids. Long-chain non-coding RNAs (lncRNAs) have many important physiological functions in eukaryotes, which include regulating gene expression, chromosome silencing, and nuclear transport. However, changes in the expression of lncRNAs in muscle cells during adipogenic transdifferentiation have not been investigated to date. Here, C2C12 myoblasts were seeded and then induced to undergo myogenic and adipogenic transdifferentiation. The expression profiles of lncRNAs in various differentiated cells were analyzed and then compared by digital gene expression (DGE) RNA sequencing. A total of 114 core lncRNAs from 836 differentially expressed lncRNAs in adipogenic cells were identified. Further investigation by in silico analysis revealed that the target genes of core lncRNAs significantly enriched various signaling pathways that were related to glucose and lipid metabolism and muscle growth. The lncRNA-GM43652 gene was a potential regulator of adipogenesis in muscle cells. It showed the highest levels of expression in adipogenic cells, and the knocking down lncRNA-GM43652 negatively influenced lipid deposition in transdifferentiated myoblasts. This study has identified the novel candidate regulators that may be assessed in future molecular studies on adipogenic conversion of muscle cells.

Highlights

  • Transdifferentiation is the transformation of one cell type to another

  • We aimed to identify the Long-chain non-coding RNAs (lncRNAs) that are involved in the adipogenic transformation of muscle cells to reveal the molecular mechanism of transdifferentiation

  • The adipogenic transdifferentiated cells gradually became round via adipogenic induction, with numerous small lipid droplets inside the cells. qRT-PCR detected the key regulatory factors that are related to myogenesis or adipogenesis in different cells (Figure 1B,C)

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Summary

Introduction

Transdifferentiation is the transformation of one cell type to another. Myoblasts have the potential to transdifferentiate into adipocytes or adipocyte-like cells under specific induction conditions (i.e., drug stimulation, cytokine treatment) [1,2,3,4,5,6]. Skeletal muscle satellite cells in humans and animals retain broad differentiation capacity, including the generation of adipocytes in an adipogenic medium in a process that the insulin sensitizer—rosiglitazone—enhances [7]. A few skeletal muscle cells could be replaced by fat cells during regeneration in humans [9]. During skin wound healing in mice, the regeneration of hair follicles is accompanied by the transformation of numerous myofibers (myofibroblasts) into white adipocytes [10]. The BMP signaling pathway is activated, which in turn drives the transformation of “myofibroblast-adipocytes” [10]

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