General Information

Video

Unit 1 - JRG Reprogramming

Objectives

The laboratory works on the reprogramming of somatic cells from mouse, pigs, and humans into pluripotent cells, the characterization the reprogrammed cells with regard to spontaneous and targeted differentiation and the suitability of the cells derived thereof in novel cell and gene therapeutic strategies. This will include the efficient generation of lympho-hematopoietic and cardiogenic tissue for use in reparative therapies, the establishment of robust gene transfer protocols for these cells, as well as the evaluation of these concepts in relevant in vivo murine and large animal models.

Research Focus

Excisable integrating and non-integrating vectors will be used to deliver the reprogramming factors to the target cells. This constitutes a crucial prerequisite to avoid tumor formation when later using iPS cells in cell therapies. The reprogrammed cells are characterized for their expression of pluripotent markers, the DNA-methylation profile of stemness related genes and and the chromatin modification patterns using bisulfite sequencing and chromatin assays. Additionally the role of DNA-repair and DNA methylation/chromatin modification in the maintenance of genetic stability and pluripotency of cells generated by iPS or somatic cell nuclear transfer (SCNT) technology is investigated. In addition, somatic nuclear transfer (SCNT) will be used to create homologoues pig models in which the therapeutic potential of reprogrammed cells can be studied.

Collaborations

• Tobias Cantz, Rebirth, MHH Hannover and Axel Schambach, Institute of Exp. Hematology, MHH Hannover: Development of a joint platform for iPS generation in the murine and human system utilizing fibroblasts or hematopoietic cells as targets
• Christopher Baum, Institute of Exp. Hematology, MHH Hannover: Genetic modification of hematopoietic stem cells
• Ute Modlich, Institute of Exp. Hematology, MHH Hannover: Generation of humanized models for the analysis of genotoxicity in hematopoietic cell gene therapy and IPSC-based gene therapy of Mpl deficiency
• Dagmar Dilloo, Children’s Hospital, University of Bonn: Reprogramming of pediatric tumor cells as models for cancer stem cells
• Hartmut Geiger, Stem Cell Center, University of Ulm: Analysis of genotoxicity during reprogramming events and directed differentiation of iPSCs
• James Adjaye and Hans Lehrach, Max Planck Institute for Molecular Genomics, Berlin: Molecular profiles of bovine and human embryonic stem cells and blastocysts
• David Williams, Children's Hospital, Harvard Medical School: Gene Transfer of DNA repair proteins to hematopoietic stem cells to induce cytotoxic drug resistance
• Tobias Brambrink, Whitehead Institute, Cambridge, Boston, MA, USA: Gene expression analysis in embryonic stem cells and iPS
• Phillippe Collas, University of Oslo, Norway: Analysis of epigenetic reprogramming using quantitative chromatin immunoprecipitation
• Epiontis, Berlin: Use of specific bisulfite technology for analysis of DNA methylation in early bovine embryos
• Sangamo, San Francisco. CA, USA: The use of zinc finger proteins for inducing homologous recombination in pigs

Further Research Projects

• Consortium: Induced pluripotent stem cells in large animal models (IPSILAM), BMBF research programm “Isolation and generation of pluri- and multipotent stem cells” (coordinator: H.Niemann)
• Consortium: Pluripotent cells for heart therapies, BMBF research programm “Cell based regenerative medicine” (H. Niemann)
• Analysis of epigenetic reprogramming and imprinting in bovine oocytes, DFG TransRegio research group Germ Cell Potential (H. Niemann)
• Production of multi-transgenic pigs for xenotransplantation, DFG TransRegio research group Xenotransplantation (H. Niemann)
• Associated Member of DFG special programm 1230 „Mechanisms of Gene Vector Entry and Persistence” (T. Moritz)

Teaching

• Hannover Biomedical Research School (HBRS) at Hannover Medical School (MHH) (Seminars and Tutorials)

Equipment and Service Facilities

[Please find a list of all available equipment here]

Publications

[Please find the publications of this workgroup here]

Staff