4.6 Article

TGF-β1 controls porcine granulosa cell states: A miRNA-mRNA network view

Journal

THERIOGENOLOGY
Volume 160, Issue -, Pages 50-60

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.theriogenology.2020.11.001

Keywords

Pig; Granulosa cells; TGF-beta 1; RNA-Seq; miRNA-mRNA network

Funding

  1. Qing Lan Project of Jiangsu Province (2020)
  2. National Natural Science Foundation of China [31772568]

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This study revealed the regulatory mechanism of TGF-beta 1 on porcine granulosa cell states, identified multiple signaling pathways regulating cell states, and potential therapeutic RNA molecules.
TGF-beta 1, an important multi-functional cytokine of the TGF-beta signaling pathway, has been reported to be crucial for ovarian granulosa cell (GC) states and female fertility. However, the molecular mechanism underlying TGF-beta 1 regulation of GC states remains largely unknown. Here, we provide a comprehensive transcriptomic view on TGF-beta 1 regulation of cell states in porcine GCs. We first confirmed that TGF-beta 1 can control GC states (apoptosis and proliferation) in pig ovary. RNA-seq showed that 909 differentially expressed genes (DEGs), including 890 DEmRNAs and 19 DEmiRNAs, were identified in TGF-beta 1-treated porcine GCs. Functional annotation showed that these DEGs were mainly involved in regulating cell states. In addition, multiple hub genes were identified by constructing the protein-protein interaction network, DEmiRNA-DEmRNAs regulatory network, and gene-pathway-function co-expression networks, which were further found to be enriched in FoxO, TGF-beta, Wnt, PIK3-Akt, p53 and Ras signaling pathways that play important roles in regulating cell states, cell cycle, proliferation, stress-responses and inflammation. The current research deeply reveals the effects of TGF-beta 1 on porcine GCs, and also identifies potential therapeutic RNA molecules for inhibiting and rescuing female infertility. (C) 2020 Elsevier Inc. All rights reserved.

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