Reprogramming and somatic memory in ES cell/hematopoietic stem cell hybrids

• Applicant: Professor Dr. Martin Zenke
• Subject Area: Cell Biology
• Term: from 2008 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 66066327

• Final Report Year: 2014

Final Report Abstract

In this project we studied two reprogramming strategies for generating pluripotent cells: (i) cell fusion with ES cells (or iPS cells) and (ii) transduction with reprogramming transcription factors to generate iPS cells. First, ES cells or iPS cells were fused with hematopoietic stem cells (HSC) to generate ES cell hybrids or iPS cell hybrids, respectively. We fund that HSC impact on differentiation kinetics and propensity of ES cell hybrids and iPS cell hybrids, which we attribute to somatic memory. Mechanistically, enhanced NODAL signaling in iPS cell hybrids caused differentiation efficiently towards mesendodermal lineages. Second, we generated iPS cells from immune-privileged Sertoli cells of testis (Ser-iPS cells). Ser-iPS cells showed reduced immunogenicity in vitro and in vivo, which we attribute to somatic memory. We suggest that taking advantage of somatic memory in reprogrammed pluripotent cells is an effective strategy for influencing their differentiation potential and biological activity.

Publications

• (2011) Evaluating the potential of putative pluripotent cells derived from human testis. Stem Cells 29,1304-1309
  Ko, K., Reinhardt, P., Tapia, N., Schneider-Kramann, R., Araúzo-Bravo, M.J., Han, D. W., Greber, B., Kim, J., Kliesch, S., Zenke, M., Schöler, H. R.
  
• (2012). Polycomb group protein Bmi1 promotes hematopoietic cell development from embryonic stem cells. Stem Cells Dev. 21, 121-132
  Ding, X., Lin, Q., Ensenat-Waser, R., Rose-John, S., and Zenke, M.
  
• (2013). Analysis of genome-wide DNA methylation profiles by BeadChip technology. Methods Mol. Biol.1049, 21-33
  Lin, Q., Wagner, W., and Zenke, M.
  
• (2014). Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells. Stem Cells Dev., 2014 Jul 8
  Qin, J., Sontag, S., Lin, Q., Mitzka, S., Leisten I., Schneider, R. K., Wang, X., Jauch, A., Peitz, M., Brüstle, O., Wagner, W., Zhao, R. C., and Zenke, M.
  
• (2014). PCGF6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ES cells and functions in iPS reprogramming. Stem Cells, 2014 Sep 3
  Zdzieblo, D., Li, X., Lin, Q., Zenke, M., Illich, D. J., Becker, M. and Müller, A. M.
  
• (2014). Polycomb protein EED is required for silencing of pluripotency genes upon ES cell differentiation. Stem Cell Rev., 2014 Aug 19
  Obier, N., Lin, Q., Cauchy, P., Hornich, V., Zenke, M., Becker, M., and Müller, A. M.
  
• (2014). Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells. PLoS ONE 9, e106110
  Wang, X., Qin, J., Zhao, R. C., and Zenke, M.
  
• (2014). The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation. Stem Cells Dev. 23, 931-940
  Ding, X., Wang, X., Sontag, S., Qin, J., Wanek, P., Lin, Q., and Zenke, M.