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Specific Gene Signatures and Pathways in Mesodermal Cells and Their Derivatives Derived from Embryonic Stem Cells

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Abstract

The vertebrate early stage embryo is consisting of the three primary germ layers ectoderm, mesoderm and endoderm, from which all organ tissues are developed. During early embryonic development, mesodermal cells become sequentially determined to more precisely defined cell types including muscle, heart, vasculature, blood, kidney, gonads, dermis and cartilage. How the prospective mesodermal cells integrate the various signals they receive and how they resolve this information to regulate their morphogenetic behavior and cell fate decisions is largely unknown. Understanding of this complex phenomenon is essential to induce selective differentiation of pluripotent stem cells into clinically relevant, physiologically functional cells such as cardiomyocytes or for transdifferentiation of easily accessible cell types such as fibroblasts into other clinically relevant cell types for applications such as cell replacement therapy, accelerated drug discovery and drug toxicological testing. This demands an in-depth analysis of the mesodermal endogenous signaling cascades and transcription factor networks. Emerging results from isolation and transcriptome characterization of pure mesodermal cells derived from murine embryonic stem cells define the genetic and cellular identity of mesodermal cells and allows a comprehensive analysis of the very dynamic process of mesodermal patterning which would not be technically feasible with conventional embryology methods.

This review focuses on defining the transcriptomic signatures of mesodermal cells and their lineages with special reference to the molecular and signaling pathways associated with the complex process of mesodermal patterning.

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Acknowledgement

This work was supported by a grant from the European Community (6th Framework Programme, Thematic Priority: Life sciences, genomics and biotechnology for health; contract no: FunGenES LSHG-CT-2003-503494).

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The authors declare no potential conflicts of interest.

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Author notes

  1. Michael Xavier Doss

    Present address: Stem Cell Center, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA

Authors and Affiliations

  1. Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931, Cologne, Germany

    Michael Xavier Doss, John Antonydas Gaspar, Johannes Winkler, Jürgen Hescheler & Agapios Sachinidis

  2. Max-Delbrück-Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany

    Herbert Schulz

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Supplementary Table 1

Enriched Gene ontology annotations in k means clusters (XLS 289 kb)

Supplementary Figure 1

KEGGanim tool is used to color the pathway members (genes) at these three KEGG pathways; Wnt signaling Pathway, TGFβ signaling pathway and Hedgehog signaling pathways. The genes are colored red and green according to their expression signal values as found at the dataset having all the five pure populations such as αMHC+ cardiomyocytes, BMP2+ and Brachyury+ mesodermal cells, CD31+ endothelial-like and Acta2+ smooth cells. The red color indicates the high expression signal and green the low expression signal. If several probesets or proteins match a pathway member, the corresponding node is split into smaller colored areas to reflect different experimental values [51]. (PPT 585 kb)

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Doss, M.X., Gaspar, J.A., Winkler, J. et al. Specific Gene Signatures and Pathways in Mesodermal Cells and Their Derivatives Derived from Embryonic Stem Cells. Stem Cell Rev and Rep 8, 43–54 (2012). https://doi.org/10.1007/s12015-011-9263-5

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