Cardiac differentiation of mouse embryonic stem cells is influenced by a PPAR γ/PGC-1α-FNDC5 pathway during the stage of cardiac precursor cell formation.
Peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α (PGC-1α) up-regulation induces FNDC5 expression in muscle and consequently causes browning of white adipose tissue (WAT). In addition to skeletal muscle, FNDC5 is mainly expressed in heart and brain tissues. Here, we demonstrate that FNDC5 expression increased during the process of cardiac differentiation of mouse embryonic stem cells (mESCs) similar to PGC-1α and PPARα. To testify the correlation between PGC-1α and FNDC5 in cardiac cell differentiation of mESCs, we utilized specific PPARγ agonist and antagonist in two stages of cardiac differentiation, during and post-cardiac precursor cells (CPCs) formation. Our results indicated that a reduction in PGC-1α expression, via treatment with GW9662 during CPCs formation stage, down-regulated FNDC5 transcript levels as well as mitochondrial markers which negatively influenced on the whole process of cardiac differentiation efficiency. On the other hand, increase PGC-1α expression during CPCs formation stage via rosiglitazone treatment increase FNDC5 and mitochondrial markers transcript levels which enhanced cardiac differentiation efficiency. Importantly, such alteration in PGC-1α expression at post-CPCs formation stage did not affect overall cardiac differentiation rate as expression of FNDC5 and mitochondrial markers were not significantly changed. We concluded that PPARγ agonist and antagonist induced up and down-regulation of PGC-1α and subsequently modulated the process of CPCs formation through an alteration in FNDC5 and mitochondrial markers expression.
Department of Medical Genetic, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Treatment and Health Services of Yazd, Yazd, Iran; Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Faezeh Ghazvini
FG
Zadegan
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran. Electronic address: kamranghaedi@royaninstitute.org.
Kamran
K
Ghaedi
Department of Medical Genetic, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences Treatment and Health Services of Yazd, Yazd, Iran.
Seyed Mehdi
SM
Kalantar
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Maryam
M
Peymani
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Motahare-Sadat
MS
Hashemi
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
Hossein
H
Baharvand
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: mh_nasr@royaninstitute.org.
Mohammad Hossein
MH
Nasr-Esfahani
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000166:cytology*; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D015415:Biomarkers; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D001205:Ascorbic Acid
Cardiac differentiation; FNDC5; GW9662; PGC-1α; PPAR γ; Rosiglitazone