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

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

DFG Programme Priority Programmes
Subproject of SPP 1356:  Pluripotency and Cellular Reprogramming