Cyclosporin a induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells

Seung Cheol Choi, Hyunjoo Lee, Ji Hyun Choi, Jong Ho Kim, Chi Yeon Park, Hyung Joon Joo, Jae Hyoung Park, Soon Jun Hong, Cheol Woong Yu, Do-Sun Lim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Little is known about the mechanisms underlying the effects of Cyclosporin A (CsA) on the fate of stem cells, including cardiomyogenic differentiation. Therefore, we investigated the effects and the molecular mechanisms behind the actions of CsA on cell lineage determination of P19 cells. CsA induced cardiomyocyte-specific differentiation of P19 cells, with the highest efficiency at a concentration of 0.32 μM during embryoid body (EB) formation via activation of the Wnt signaling pathway molecules, Wnt3a, Wnt5a, and Wnt8a, and the cardiac mesoderm markers, Mixl1, Mesp1, and Mesp2. Interestingly, cotreatment of P19 cells with CsA plus dimethyl sulfoxide (DMSO) during EB formation significantly increases cardiac differentiation. In contrast, mRNA expression levels of hematopoietic and endothelial lineage markers, including Flk1 and Er71, were severely reduced in CsA-treated P19 cells. Furthermore, expression of Flk1 protein and the percentage of Flk1+ cells were severely reduced in 0.32 μM CsA-treated P19 cells compared to control cells. CsA significantly modulated mRNA expression levels of the cell cycle molecules, p53 and Cyclins D1, D2, and E2 in P19 cells during EB formation. Moreover, CsA significantly increased cell death and reduced cell number in P19 cells during EB formation. These results demonstrate that CsA induces cardiac differentiation but inhibits hemato-endothelial differentiation via activation of the Wnt signaling pathway, followed by modulation of cell lineage-determining genes in P19 cells during EB formation.

Original languageEnglish
Article numbere0117410
JournalPLoS One
Volume10
Issue number1
DOIs
Publication statusPublished - 2015 Jan 28

Fingerprint

cyclosporins
cell differentiation
Cyclosporine
cyclosporine
Cell Differentiation
Embryoid Bodies
cells
Wnt Signaling Pathway
Cell Lineage
Chemical activation
Cyclin D2
Messenger RNA
Molecules
Cyclin D1
Mesoderm
Cell death
Dimethyl Sulfoxide
Stem cells
Cardiac Myocytes
Cell Cycle

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cyclosporin a induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells. / Choi, Seung Cheol; Lee, Hyunjoo; Choi, Ji Hyun; Kim, Jong Ho; Park, Chi Yeon; Joo, Hyung Joon; Park, Jae Hyoung; Hong, Soon Jun; Yu, Cheol Woong; Lim, Do-Sun.

In: PLoS One, Vol. 10, No. 1, e0117410, 28.01.2015.

Research output: Contribution to journalArticle

Choi, Seung Cheol ; Lee, Hyunjoo ; Choi, Ji Hyun ; Kim, Jong Ho ; Park, Chi Yeon ; Joo, Hyung Joon ; Park, Jae Hyoung ; Hong, Soon Jun ; Yu, Cheol Woong ; Lim, Do-Sun. / Cyclosporin a induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells. In: PLoS One. 2015 ; Vol. 10, No. 1.
@article{37057b8311e2445284ea72bea9809d65,
title = "Cyclosporin a induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells",
abstract = "Little is known about the mechanisms underlying the effects of Cyclosporin A (CsA) on the fate of stem cells, including cardiomyogenic differentiation. Therefore, we investigated the effects and the molecular mechanisms behind the actions of CsA on cell lineage determination of P19 cells. CsA induced cardiomyocyte-specific differentiation of P19 cells, with the highest efficiency at a concentration of 0.32 μM during embryoid body (EB) formation via activation of the Wnt signaling pathway molecules, Wnt3a, Wnt5a, and Wnt8a, and the cardiac mesoderm markers, Mixl1, Mesp1, and Mesp2. Interestingly, cotreatment of P19 cells with CsA plus dimethyl sulfoxide (DMSO) during EB formation significantly increases cardiac differentiation. In contrast, mRNA expression levels of hematopoietic and endothelial lineage markers, including Flk1 and Er71, were severely reduced in CsA-treated P19 cells. Furthermore, expression of Flk1 protein and the percentage of Flk1+ cells were severely reduced in 0.32 μM CsA-treated P19 cells compared to control cells. CsA significantly modulated mRNA expression levels of the cell cycle molecules, p53 and Cyclins D1, D2, and E2 in P19 cells during EB formation. Moreover, CsA significantly increased cell death and reduced cell number in P19 cells during EB formation. These results demonstrate that CsA induces cardiac differentiation but inhibits hemato-endothelial differentiation via activation of the Wnt signaling pathway, followed by modulation of cell lineage-determining genes in P19 cells during EB formation.",
author = "Choi, {Seung Cheol} and Hyunjoo Lee and Choi, {Ji Hyun} and Kim, {Jong Ho} and Park, {Chi Yeon} and Joo, {Hyung Joon} and Park, {Jae Hyoung} and Hong, {Soon Jun} and Yu, {Cheol Woong} and Do-Sun Lim",
year = "2015",
month = "1",
day = "28",
doi = "10.1371/journal.pone.0117410",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Cyclosporin a induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells

AU - Choi, Seung Cheol

AU - Lee, Hyunjoo

AU - Choi, Ji Hyun

AU - Kim, Jong Ho

AU - Park, Chi Yeon

AU - Joo, Hyung Joon

AU - Park, Jae Hyoung

AU - Hong, Soon Jun

AU - Yu, Cheol Woong

AU - Lim, Do-Sun

PY - 2015/1/28

Y1 - 2015/1/28

N2 - Little is known about the mechanisms underlying the effects of Cyclosporin A (CsA) on the fate of stem cells, including cardiomyogenic differentiation. Therefore, we investigated the effects and the molecular mechanisms behind the actions of CsA on cell lineage determination of P19 cells. CsA induced cardiomyocyte-specific differentiation of P19 cells, with the highest efficiency at a concentration of 0.32 μM during embryoid body (EB) formation via activation of the Wnt signaling pathway molecules, Wnt3a, Wnt5a, and Wnt8a, and the cardiac mesoderm markers, Mixl1, Mesp1, and Mesp2. Interestingly, cotreatment of P19 cells with CsA plus dimethyl sulfoxide (DMSO) during EB formation significantly increases cardiac differentiation. In contrast, mRNA expression levels of hematopoietic and endothelial lineage markers, including Flk1 and Er71, were severely reduced in CsA-treated P19 cells. Furthermore, expression of Flk1 protein and the percentage of Flk1+ cells were severely reduced in 0.32 μM CsA-treated P19 cells compared to control cells. CsA significantly modulated mRNA expression levels of the cell cycle molecules, p53 and Cyclins D1, D2, and E2 in P19 cells during EB formation. Moreover, CsA significantly increased cell death and reduced cell number in P19 cells during EB formation. These results demonstrate that CsA induces cardiac differentiation but inhibits hemato-endothelial differentiation via activation of the Wnt signaling pathway, followed by modulation of cell lineage-determining genes in P19 cells during EB formation.

AB - Little is known about the mechanisms underlying the effects of Cyclosporin A (CsA) on the fate of stem cells, including cardiomyogenic differentiation. Therefore, we investigated the effects and the molecular mechanisms behind the actions of CsA on cell lineage determination of P19 cells. CsA induced cardiomyocyte-specific differentiation of P19 cells, with the highest efficiency at a concentration of 0.32 μM during embryoid body (EB) formation via activation of the Wnt signaling pathway molecules, Wnt3a, Wnt5a, and Wnt8a, and the cardiac mesoderm markers, Mixl1, Mesp1, and Mesp2. Interestingly, cotreatment of P19 cells with CsA plus dimethyl sulfoxide (DMSO) during EB formation significantly increases cardiac differentiation. In contrast, mRNA expression levels of hematopoietic and endothelial lineage markers, including Flk1 and Er71, were severely reduced in CsA-treated P19 cells. Furthermore, expression of Flk1 protein and the percentage of Flk1+ cells were severely reduced in 0.32 μM CsA-treated P19 cells compared to control cells. CsA significantly modulated mRNA expression levels of the cell cycle molecules, p53 and Cyclins D1, D2, and E2 in P19 cells during EB formation. Moreover, CsA significantly increased cell death and reduced cell number in P19 cells during EB formation. These results demonstrate that CsA induces cardiac differentiation but inhibits hemato-endothelial differentiation via activation of the Wnt signaling pathway, followed by modulation of cell lineage-determining genes in P19 cells during EB formation.

UR - http://www.scopus.com/inward/record.url?scp=84961292047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961292047&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0117410

DO - 10.1371/journal.pone.0117410

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0117410

ER -