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Comparative expression analysis of Shox2 -deficient embryonic stem cell-derived sinoatrial node-like cells

Hoffmann, Sandra; Schmitteckert, Stefanie; Griesbeck, Anne; Preiss, Hannes; Sumer, Simon; Rolletschek, Alexandra 1; Granzow, Martin; Eckstein, Volker; Niesler, Beate; Rappold, Gudrun A.
1 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)

Abstract:

The homeodomain transcription factor Shox2 controls the development and function of the native cardiac pacemaker, the sinoatrial node (SAN).Moreover, SHOX2 mutations have been associatedwith cardiac arrhythmias in humans. For detailed examination of Shox2-dependent developmentalmechanisms in SAN cells, we established a murine embryonic stem cell (ESC)-based model using Shox2 as a molecular tool. Shox2+/+ and Shox2−/− ESC clones were isolated and differentiated according to five different protocols in order to evaluate the most efficient enrichment of SAN-like cells. Expression analysis of cell subtype-specific marker genes revealed most efficient enrichment after CD166-based cell sorting. Comparative cardiac expression profiles of Shox2+/+ and Shox2−/− ESCs were examined by nCounter technology. Among other genes, we identified Nppb as a novel putative Shox2 target during differentiation in ESCs. Differential expression of Nppb could be confirmed in heart tissue of Shox2−/− embryos. Taken together, we established an ESC-based cardiac differentiation model and successfully purified Shox2+/+ and Shox2−/− SAN-like cells. This now provides an excellent basis for the investigation of molecular mechanisms under physiological and pathophysiological conditions for evaluating novel therapeutic approaches.


Verlagsausgabe §
DOI: 10.5445/IR/1000079722
Originalveröffentlichung
DOI: 10.1016/j.scr.2017.03.018
Scopus
Zitationen: 8
Web of Science
Zitationen: 8
Dimensions
Zitationen: 8
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 05.2017
Sprache Englisch
Identifikator ISSN: 1873-5061, 1876-7753
urn:nbn:de:swb:90-797225
KITopen-ID: 1000079722
HGF-Programm 47.02.01 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-1
Erschienen in Stem cell research
Verlag Elsevier
Band 21
Seiten 51–57
Vorab online veröffentlicht am 29.03.2017
Schlagwörter Shox2, Mouse embryonic stem cells, Transgenic cells, Differentiation model, Sinoatrial node-like cells
Nachgewiesen in Dimensions
Scopus
Web of Science
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