Stem Cell Engineering Laboratory
Somatic cells can be reprogrammed to a pluripotent embryonic stem cell-like state (induced pluripotent stem (iPS) cells) by combinations of the transcription factors OCT4, SOX2, NANOG, LIN28, KLF4 and cMYC (Takahashi et al., 2006, 2007, Cell, Yu et al., 2007, Science, Park et al., 2007, Nature). The initial studies were underdone inducing pluripotency in mouse and human fibroblasts. We were able to demonstrate, that mouse and human neural stem cells, that express SOX2, KLF4 and cMYC, can be reprogrammed to iPS cells by retroviral expression of OCT4 (Kim et al., 2008, 2009, Nature). Our initial finding, that multipotent neural stem cells are more amenable to reprogramming, could be further validated with hematopoietic and endodermal progenitor cells.
Cord blood derived cells are attractive starting populations for reprogramming, since their DNA is relatively young and they present the perspective to generate HLA-matched cell grafts based on existing cord blood banks. We have derived iPS cells from human cord blood derived CD34+ stem/progenitor cells and mesenchymal stroma cell populations. These iPS cells are highly similar to human embryonic stem cells morphologically, at the molecular level by gene expression microarrays, global miRNA and epigenetic profiling, as well as in their in vitro and in vivo differentiation. We are focusing on the hematopoietic and erythroid as well as neural differentiation potential of our human blood stem cell derived iPS cells.
Our laboratory serves as a ‘Stem Cell Engineering’ core facility to the institute and beyond. We have trained multiple students and postdoctoral fellows on mouse and human iPS cell generation and cultivation. We are developing and evaluating different approaches to reprogram somatic cells to pluripotency or multipotency. Retroviral and lentiviral vectors are the most effective and efficient way to transfer and express reprogramming factors when generating iPS cells. The usage of episomal expression vectors and RNA transfer for cellular reprogramming as well as genome editing and genetic lineage selection strategies are the foundation to model diseases in vitro using patient-specific induced pluripotent stem cells.
We are further coordinating the collaborative research efforts of the Max Planck Institute for Molecular Biomedicine with the Max Planck partner groups at the UNIST, Ulsan and Konkuk University, Seoul, South Korea.
Dorn, I., Klich, K., Arauzo-Bravo, M.J., Radstaak, M., Santourlidis, S., Ghanjati, F., Radke, T., Psathaki, O.E., Hargus, G., Kramer, J., Einhaus, M., Kim, J.B., Kögler, G., Wernet, P., Schöler, H.R., Schlenke, P., Zaehres, H. (2015) Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin. Haematologica 100, 32-41
Hargus, G., Ehrlich, M., Arauzo-Bravo, M.J., Hemmer, K., Hallman, A.L., Reinhardt, P., Kim, K.P., Adachi, K., Santourlidis, S., Ghanjati, F., Fauser, M., Ossig, C., Storch, A., Kim, J.B., Schwamborn, J.C., Sterneckert, J., Schöler, H.R., Kuhlmann, T., Zaehres, H. (2014) Origin dependent neural cell identities in differentiated human induced pluripotent stem cells in vitro and after transplantation into the rodent brain. Cell Reports 8, 1697-703
Han, D.W., Tapia., N., Hermann, A., Hemmer, K., Höing, S., Arauzo-Bravo, M.J., Zaehres, H., Wu, G., Frank, S., Moritz, S., Greber, B., Yang, J.H., Schwamborn, J., Storch, A., Schöler, H.R. (2012) Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell 10, 465-472
Kim, J.B., Greber, B., Arauzo-Bravo, M.J., Meyer, J., Park, K.I., Zaehres, H., Schöler, H.R. (2009) Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649-653
Kim, J.B.*, Zaehres, H.*, Wu, G., Gentile, L., Ko, K., Sebastiano, V., Arauzo-Bravo, M.J., Ruau, D., Han, D.W., Zenke, M., Schöler, H.R. (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454, 646-650
Zaehres, H., Schöler, H.R. (2007) Induction of pluripotency: from mouse to human. Cell 131, 834-835
Zaehres, H., Lensch, M.W., Daheron, L., Stewart, S.A., Itskovitz-Eldor, J., Daley, G.Q. (2005) High-efficiency RNA interference in human embryonic stem cells. Stem Cells 23, 299-305
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