Article

Parallel Differentiation of Embryonic Stem Cells into Different Cell Types by a Single Gene-Based Differentiation System

University of Wuerzburg, Physiological Chemistry I, Biocenter, Wuerzburg, Germany.
Cellular reprogramming 03/2012; 14(2):106-11. DOI: 10.1089/cell.2011.0067
Source: PubMed

ABSTRACT The generation of defined somatic cell types from pluripotent stem cells represents a promising system for many applications for regenerative therapy or developmental studies. Certain key developmental genes have been shown to be able to influence the fate determination of differentiating stem cells suggesting an alternative differentiation strategy to conventional medium-based methods. Here, we present a system allowing controlled, directed differentiation of embryonic stem cells (ESCs) solely by ectopic expression of single genes. We demonstrate that the myogenic master regulator myoD1 is sufficient to induce formation of skeletal muscle. In contrast to previous studies, our data suggest that myoD1-induced differentiation is independent of additional differentiation-inducing or lineage-promoting signals and occurs even under pluripotency-promoting conditions. Moreover, we demonstrate that single gene-induced differentiation enables the controlled formation of two distinct cell types in parallel. By mixing ES cell lines expressing myoD1 or the neural transcription factor ngn2, respectively, we generated a mixed culture of myocytes and neurons. Our findings provide new insights in the role of key developmental genes during cell fate decisions. Furthermore, this study represents an interesting strategy to obtain mixed cultures of different cells from stem cells, suggesting a valuable tool for cellular development and cell-cell interaction studies.

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    • "We suggest that this approach can be extended to generate other cell types if the appropriate TFs are identified. Indeed, we were recently able to use this approach for the generation of myoblasts by ectopic expression of MyoD1 [51]. Importantly, this process could be combined with the here presented Ngn2-induced differentiation allowing the formation of neurons and myoblasts in parallel. "
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