BMP-SMAD signaling: From pluripotent stem cells to cardiovascular commitment

Valeria V. Orlova*, Susana Chuva de Sousa Lopes, Gudrun Valdimarsdottir

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

6 Citations (Scopus)

Abstract

Human pluripotent stem cells (hPSCs) can form all somatic cells of the body. They thus offer opportunities for understanding (i) the basic steps of early human development, (ii) the pathophysiology in human degenerative diseases and (iii) approaches to regenerative medicine and drug development. Methods for improving their differentiation to defined mesodermal derivatives in particular will benefit their use in all of these areas but most particularly applications that require cardiac and vascular tissue. However, the molecular mechanisms that regulate mesodermal development in humans are still poorly understood. Gene ablation studies in mice have shown that the signaling pathways activated by the transforming growth factor beta (TGFβ) superfamily, including the bone morphogenetic proteins (BMP), play crucial roles in mesoderm differentiation and patterning the early embryo. Understanding their interplay and interaction with other signaling pathways, how they activate and inhibit transcription factors and epigenetic regulators during self-renewal, maintenance and exit from pluripotency and differentiation could provide vital information for a range of applications. This includes disease modeling when the hPSCs are derived from patients or drug screens for diseases of mesodermal organs. Here, we review the role of the BMP-SMAD signaling pathway in pluripotent stem cells and during mesoderm differentiation with focus on the cells that make up the cardiovascular system.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalCytokine and Growth Factor Reviews
Volume27
DOIs
Publication statusPublished - 1 Feb 2016

Bibliographical note

Funding Information:
Susana M. Chuva de Sousa Lopes , PhD is Associate Professor in the Dept. of Anatomy and Embryology at the Leiden University Medical Center, Leiden the Netherlands. She was appointed Guest Professor at the Dept. Reproductive Medicine, University Ghent, Belgium in 2013. Her laboratory focuses on investigating the developmental trajectories of human organs and tissues, with a particular interest for the germline and associated gain-and-loss of potency and epigenetic makeup. She has investigated the role of BMP signalling in germline development in mouse and created a transgene reporter to follow BMP-SMAD signalling activation in vivo. Her lab has contributed to a better understanding of the BMP-TGFbeta signalling in the acquisition of different pluripotency states, self-renewal and differentiation of mouse and human embryonic stem cells. Dr. Chuva de Sousa Lopes’s lab is currently funded by the Belgium Interuniversity Attraction Poles-Phase VII, the Portuguese Fundação para a Ciência e Tecnologia and the Dutch Bontius Stichting. She is an elected member of the Special Interest Group “Stem Cells” and the elected Dutch national “basic scientist” representative of the European Society of Human Reproduction and Embryology (ESHRE). She is executive editor of the Elsevier journal Gene and associated editor of the Nature publishing group journal Scientific Reports.

Funding Information:
Gudrun Valdimarsdottir , PhD. is an assistant professor at the BMC, University of Iceland. She is working on human embryonic stem cell commitment towards the cardiovascular lineage with a special focus on the role of the TGFbeta superfamily. Her contribution to the field is mainly on the effect of TGFbeta and BMP members on the regulation of angiogenesis. Dr. Valdimarsdottir´s lab is funded by the University of Iceland and the Icelandic Research Center, RANNIS. She is currently a member of the ISSCR, Icelandic Cancer Society and Icelandic Science Society. She is also a project manager of the Graduate Program in Molecular Life Sciences (GPMLS) at BMC, University of Iceland.

Funding Information:
VVO is supported by European Community’s Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement no. 602423 (Plurimes); SMCSL is supported by the Interuniversity Attraction Poles-Phase VII [IUAP/PAI P7/14]; GV is supported by the University of Iceland research fund .

Publisher Copyright:
© 2015 Elsevier Ltd.

Other keywords

  • BMP-SMAD signaling
  • Cardiovascular cells
  • Embryonic stem cells
  • Hemogenic endothelium
  • Induced pluripotent stem cells
  • Mesodermal lineage
  • Pluripotent stem cells
  • Vascular endothelium

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