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 finding, that multipotent neural stem cells are more amenable to reprogramming, could be further validated with hematopoietic and endodermal progenitor cells. We have comparatively evaluated the hematopoietic and erythroid as well as neural differentiation potential of human cord blood and neural stem cell derived iPS cells (Hargus et al., 2014, Dorn et al., 2015).
Our laboratory has served 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 have evaluated different approaches to reprogram somatic cells to pluripotency or multipotency (e.g. retro/lentiviral vectors, episomal plasmids, RNA transfer).
Patient-derived induced pluripotent stem cells and their differentiation derivatives hold great promise as novel in vitro model systems to study human pathogenesis. We are currently focusing to model neural (Frontotemporal Dementia) and skeletal muscle (Duchenne, LGMD) diseases with human iPS cells and genome editing.
Hallmann A.L., Arauzo-Bravo M.J., Mavrommatis L., Ehrlich M., Röpke A., Brockhaus J., Missler M., Sterneckert J., Schöler H.R., Kuhlmann T., Zaehres H*., Hargus G*. (2017) Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein. Sci Rep. 7, 42991
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
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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