Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes

Background. The role of Notch signaling pathway in the differentiation of epicardial progenitor cells (EPCs) into adipocytes is unclear. The objective is to investigate the effects of Notch signaling on the differentiation of EPCs into adipocytes. Methods. Frozen sections of C57BL/6J mouse hearts we...

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Main Authors: Bin Liu, Dinghui Wang, Tianhua Xiong, Yajie Liu, Xiaodong Jing, Jianlin Du, Qiang She
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/8859071
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author Bin Liu
Dinghui Wang
Tianhua Xiong
Yajie Liu
Xiaodong Jing
Jianlin Du
Qiang She
author_facet Bin Liu
Dinghui Wang
Tianhua Xiong
Yajie Liu
Xiaodong Jing
Jianlin Du
Qiang She
author_sort Bin Liu
collection DOAJ
description Background. The role of Notch signaling pathway in the differentiation of epicardial progenitor cells (EPCs) into adipocytes is unclear. The objective is to investigate the effects of Notch signaling on the differentiation of EPCs into adipocytes. Methods. Frozen sections of C57BL/6J mouse hearts were used to observe epicardial adipose tissue (EAT), and genetic lineage methods were used to trace EPCs. EPCs were cultured in adipogenic induction medium with Notch ligand jagged-1 or γ-secretase inhibitor DAPT. The adipocyte markers, Notch signaling, and adipogenesis transcription factors were determined. Results. There was EAT located at the atrial–ventricular groove in mouse. By using genetic lineage tracing methods, we found that EPCs were a source of epicardial adipocytes. EPCs had lipid droplet accumulation, and the expression of adipocyte markers FABP-4 and perilipin-1 was upregulated under adipogenic induction. Activating the Notch signaling with jagged-1 attenuated the adipogenic differentiation of EPCs and downregulated the key adipogenesis transcription factor peroxisome proliferator activated receptor-γ (PPAR-γ), while inhibiting the signaling promoted adipogenic differentiation and upregulated PPAR-γ. When blocking PPAR-γ, the role of Notch signaling in promoting adipogenic differentiation was inhibited. Conclusions. EPCs are a source of epicardial adipocytes. Downregulation of the Notch signaling pathway promotes the differentiation of EPCs into adipocytes via PPAR-γ.
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spelling doaj-art-e5918c9480dc47d98b6618b2f2a1252b2025-02-03T06:46:01ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/88590718859071Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into AdipocytesBin Liu0Dinghui Wang1Tianhua Xiong2Yajie Liu3Xiaodong Jing4Jianlin Du5Qiang She6Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaBackground. The role of Notch signaling pathway in the differentiation of epicardial progenitor cells (EPCs) into adipocytes is unclear. The objective is to investigate the effects of Notch signaling on the differentiation of EPCs into adipocytes. Methods. Frozen sections of C57BL/6J mouse hearts were used to observe epicardial adipose tissue (EAT), and genetic lineage methods were used to trace EPCs. EPCs were cultured in adipogenic induction medium with Notch ligand jagged-1 or γ-secretase inhibitor DAPT. The adipocyte markers, Notch signaling, and adipogenesis transcription factors were determined. Results. There was EAT located at the atrial–ventricular groove in mouse. By using genetic lineage tracing methods, we found that EPCs were a source of epicardial adipocytes. EPCs had lipid droplet accumulation, and the expression of adipocyte markers FABP-4 and perilipin-1 was upregulated under adipogenic induction. Activating the Notch signaling with jagged-1 attenuated the adipogenic differentiation of EPCs and downregulated the key adipogenesis transcription factor peroxisome proliferator activated receptor-γ (PPAR-γ), while inhibiting the signaling promoted adipogenic differentiation and upregulated PPAR-γ. When blocking PPAR-γ, the role of Notch signaling in promoting adipogenic differentiation was inhibited. Conclusions. EPCs are a source of epicardial adipocytes. Downregulation of the Notch signaling pathway promotes the differentiation of EPCs into adipocytes via PPAR-γ.http://dx.doi.org/10.1155/2021/8859071
spellingShingle Bin Liu
Dinghui Wang
Tianhua Xiong
Yajie Liu
Xiaodong Jing
Jianlin Du
Qiang She
Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
Stem Cells International
title Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
title_full Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
title_fullStr Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
title_full_unstemmed Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
title_short Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes
title_sort inhibition of notch signaling promotes the differentiation of epicardial progenitor cells into adipocytes
url http://dx.doi.org/10.1155/2021/8859071
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