Mixl1 and Flk1 Are Key Players of Wnt/TGF-β Signaling During DMSO-Induced Mesodermal Specification in P19 cells

Seung Cheol Choi, Ji Hyun Choi, Long Hui Cui, Ha Rim Seo, 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

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Abstract

Dimethyl sulfoxide (DMSO) is widely used to induce multilineage differentiation of embryonic and adult progenitor cells. To date, little is known about the mechanisms underlying DMSO-induced mesodermal specification. In this study, we investigated the signaling pathways and lineage-determining genes involved in DMSO-induced mesodermal specification in P19 cells. Wnt/β-catenin and TGF-β superfamily signaling pathways such as BMP, TGF-β and GDF1 signaling were significantly activated during DMSO-induced mesodermal specification. In contrast, Nodal/Cripto signaling pathway molecules, required for endoderm specification, were severely downregulated. DMSO significantly upregulated the expression of cardiac mesoderm markers but inhibited the expression of endodermal and hematopoietic lineage markers. Among the DMSO-activated cell lineage markers, the expression of Mixl1 and Flk1 was dramatically upregulated at both the transcript and protein levels, and the populations of Mixl1+, Flk1+ and Mixl1+/Flk1+ cells also increased significantly. DMSO modulated cell cycle molecules and induced cell apoptosis, resulting in significant cell death during EB formation of P19 cells. An inhibitor of Flk1, SU5416 significantly blocked expressions of TGF-β superfamily members, mesodermal cell lineage markers and cell cycle molecules but it did not affect Wnt molecules. These results demonstrate that Mixl1 and Flk1 play roles as key downstream or interacting effectors of Wnt/TGF-β signaling pathway during DMSO-induced mesodermal specification in P19 cells.

Original languageEnglish
Pages (from-to)1807-1821
Number of pages15
JournalJournal of Cellular Physiology
Volume230
Issue number8
DOIs
Publication statusPublished - 2015 Aug 1

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Dimethyl Sulfoxide
Specifications
Molecules
Cell Lineage
Cell Cycle
Cells
Catenins
Endoderm
Wnt Signaling Pathway
Mesoderm
Cell death
Cell Death
Stem Cells
Down-Regulation
Genes
Apoptosis
Population

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Mixl1 and Flk1 Are Key Players of Wnt/TGF-β Signaling During DMSO-Induced Mesodermal Specification in P19 cells. / Choi, Seung Cheol; Choi, Ji Hyun; Cui, Long Hui; Seo, Ha Rim; Kim, Jong Ho; Park, Chi Yeon; Joo, Hyung Joon; Park, Jae Hyoung; Hong, Soon Jun; Yu, Cheol Woong; Lim, Do-Sun.

In: Journal of Cellular Physiology, Vol. 230, No. 8, 01.08.2015, p. 1807-1821.

Research output: Contribution to journalArticle

Choi, Seung Cheol ; Choi, Ji Hyun ; Cui, Long Hui ; Seo, Ha Rim ; Kim, Jong Ho ; Park, Chi Yeon ; Joo, Hyung Joon ; Park, Jae Hyoung ; Hong, Soon Jun ; Yu, Cheol Woong ; Lim, Do-Sun. / Mixl1 and Flk1 Are Key Players of Wnt/TGF-β Signaling During DMSO-Induced Mesodermal Specification in P19 cells. In: Journal of Cellular Physiology. 2015 ; Vol. 230, No. 8. pp. 1807-1821.
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