空间转录组学分析：母体肥胖症损害胚胎肢体发育过程中的成肌细胞迁移和分化。

Spatial Transcriptomics Analysis: Maternal Obesity Impairs Myogenic Cell Migration and Differentiation during Embryonic Limb Development.

机构信息

Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Int J Mol Sci. 2024 Aug 31;25(17):9488. doi: 10.3390/ijms25179488.

DOI:10.3390/ijms25179488

PMID:39273445

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11395138/

Abstract

Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as , , , and , were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.

摘要

肢体肌肉负责身体活动，胚胎发生期间的成肌细胞迁移对于肢体肌肉的形成是必不可少的。母体肥胖（MO）会损害产前骨骼肌发育，但 MO 对成肌细胞迁移的影响仍有待研究。在 E13.5 收集 C57BL/6 小鼠胚胎。使用 GeoMx DSP 平台沿成肌细胞迁移路径（肌节、背/腹肢、肢体基质、肢体尖端）定制五个区域，并使用 GeomxTools 3.6.0 分析数据。MO 组共有 2224 个基因下调。GO 富集分析表明，MO 抑制了与迁移相关的生物学过程。引导成肌迁移的信号通路，如肝细胞生长因子信号、成纤维细胞生长因子信号、Wnt 信号和 GTPase 信号，在 MO E13.5 肢体尖端下调。相应地，参与成肌细胞迁移的基因，如、、、和，在 MO 组中表达下调，尤其是在肢体的背侧和腹侧。此外，MO 肢体中的成肌分化相关基因也下调。MO 阻碍胚胎肢体中成肌细胞的迁移和分化，这解释了 MO 导致胎儿肌肉发育和后代肌肉功能受损的原因。