Skip to main content
Log in

Enrichment of cardiac differentiation by a large starting number of embryonic stem cells in embryoid bodies is mediated by the Wnt11-JNK pathway

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Embryoid bodies (EBs) with large starting numbers of embryonic stem cells (ESCs) have a greater degree of cardiac differentiation than from low numbers of EBs. However, the biological roles of signaling molecules in these effects are not well understood. Here, we show that groups of EBs with different starting numbers of ESCs had differential gene expression patterns for Wnt5a and Wnt11. Wnt11 significantly increased the percentage of beating EBs by up-regulating the expression of the cardiac-specific genes. Wnt5a did not show these effects. Moreover, Wnt11 significantly increased the level of phosphorylated Jun N-terminal kinase. The inhibition of the JNK pathway by SP600125 blocked the effects of Wnt11. Thus, enrichment of cardiac differentiation in groups of EBs with a larger starting number of ESCs is mediated by the Wnt11-JNK pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Boheler KR, Czyz J, Tweedie D, Yang HT, Anisimov SV, Wobus AM (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91:189–201

    Article  CAS  PubMed  Google Scholar 

  • Chen K, Wu L, Wang ZZ (2008) Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells. J Cell Biochem 104:119–128

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Lin YQ, Xie SL, Wang JF (2010) Mitogen-activated protein kinase in endothelin-1-induced cardiac differentiation of mouse embryonic stem cells. J Cell Biochem 111:1619–1628

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Lin YQ, Xie SL, Wu HF, Wang JF (2011) Enrichment of cardiac differentiation of mouse embryonic stem cells by optimizing the hanging drop method. Biotechnol Lett 33:853–858

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Bi LL, Wang ZQ, Zhao F, Gan XD, Wang YG (2013) Time-dependent regulation of neuregulin-1beta/ErbB/ERK pathways in cardiac differentiation of mouse embryonic stem cells. Mol Cell Biochem 380:67–72

    Article  CAS  PubMed  Google Scholar 

  • Cohen ED, Miller MF, Wang Z, Moon RT, Morrisey EE (2012) Wnt5a and Wnt11 are essential for second heart field progenitor development. Development 139:1931–1940

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eisenberg CA, Gourdie RG, Eisenberg LM (1997) Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6. Development 124:525–536

    CAS  PubMed  Google Scholar 

  • Flaherty MP, Abdel-Latif A, Li Q, Hunt G, Ranjan S, Ou Q, Tang XL, Johnson RK, Bolli R, Dawn B (2008) Noncanonical Wnt11 signaling is sufficient to induce cardiomyogenic differentiation in unfractionated bone marrow mononuclear cells. Circulation 117:2241–2252

    Article  CAS  PubMed  Google Scholar 

  • Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661–680

    Article  CAS  PubMed  Google Scholar 

  • Pandur P, Lasche M, Eisenberg LM, Kuhl M (2002) Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418:636–641

    Article  CAS  PubMed  Google Scholar 

  • Park J, Cho CH, Parashurama N, Li Y, Berthiaume F, Toner M, Tilles AW, Yarmush ML (2007) Microfabrication-based modulation of embryonic stem cell differentiation. Lab Chip 7:1018–1028

    Article  CAS  PubMed  Google Scholar 

  • Rungarunlert S, Klincumhom N, Bock I, Nemes C, Techakumphu M, Pirity MK, Dinnyes A (2011) Enhanced cardiac differentiation of mouse embryonic stem cells by use of the slow-turning, lateral vessel (STLV) bioreactor. Biotechnol Lett 33:1565–1573

    Article  CAS  PubMed  Google Scholar 

  • Schroeder KE, Condic ML, Eisenberg LM, Yost HJ (1999) Spatially regulated translation in embryos: asymmetric expression of maternal Wnt-11 along the dorsal–ventral axis in Xenopus. Dev Biol 214:288–297

    Article  CAS  PubMed  Google Scholar 

  • Schukur L, Zorlutuna P, Cha JM, Bae H, Khademhosseini A (2013) Directed differentiation of size-controlled embryoid bodies towards endothelial and cardiac lineages in RGD-modified poly(ethylene glycol) hydrogels. Adv Healthc Mater 2:195–205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xiang G, Yang Q, Wang B, Sekiya N, Mu X, Tang Y, Chen CW, Okada M, Cummins J, Gharaibeh B, Huard J (2011) Lentivirus-mediated Wnt11 gene transfer enhances cardiomyogenic differentiation of skeletal muscle-derived stem cells. Mol Ther 19:790–796

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguchi TP, Bradley A, McMahon AP, Jones S (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126:1211–1223

    CAS  PubMed  Google Scholar 

  • Yang DH, Yoon JY, Lee SH, Bryja V, Andersson ER, Arenas E, Kwon YG, Choi KY (2009) Wnt5a is required for endothelial differentiation of embryonic stem cells and vascularization via pathways involving both Wnt/beta-catenin and protein kinase Calpha. Circ Res 104:372–379

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China to Ming Chen (No. 81200119) and a grant from the Fundamental Research Funds for the Central Universities to Ming Chen (No. 121007).

Supporting information

Supplementary Table 1—Primers for RT-PCR analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ming Chen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 32 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, M., Qian, C., Bi, LL. et al. Enrichment of cardiac differentiation by a large starting number of embryonic stem cells in embryoid bodies is mediated by the Wnt11-JNK pathway. Biotechnol Lett 37, 475–481 (2015). https://doi.org/10.1007/s10529-014-1700-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-014-1700-5

Keywords

Navigation