Abstract: The present invention provides means and methods for the generation of midbrain organoids which are useful for studying neurodevelopmental and neurodegenerative diseases. Neuroepithelial stem cells serve as a starting population for the generation of midbrain organoids by contacting them with differentiation medium under agitating conditions in three-dimensional cell culture comprising a matrix.

Abstract: The present invention relates to a microfluidic device (1) for cultivating cells, in particular for generating brain organoids, comprising at least two fluid channels (2) positioned essentially opposite to each other and a main chamber (3) located between the fluid channels (2), wherein the main chamber (3) comprises at least one preferably sealable access opening, and each of the at least two fluid channels (2) is fluidly connected to the main chamber (3) at at least one point of contact (4), wherein a slotted structure (5) is provided at each point of contact (4) separating the main chamber (3) from the respective fluid channel (2), wherein the slotted structure (5) is permeable to a liquid.

Abstract: The present invention relates to a method for identifying molecules promoting or inhibiting dopaminergic neuronal differentiation and/or death of dopaminergic neurons in a three-dimensional cell culture. Furthermore, the present invention relates to a method for producing dopaminergic neurons in a three-dimensional cell culture. In addition, the present invention relates to a method for segmenting an image of a cell culture.

Abstract: The present invention relates to a nucleic acid molecule at least one nucleotide sequence encoding a selection marker indicating homologous recombination in a eukaryotic cell and at least one nucleotide sequence encoding a selection marker indicating heterologous recombination in said eukaryotic cell. The present invention also relates to a composition of matter comprising at least two nucleic acid molecules of the invention. The present invention further relates to in vitro methods for enriching or producing eukaryotic cells which are modified by homologous recombination.

Abstract: The present invention provides means and methods for the generation of midbrain organoids which are useful for studying neurodevelopmental and neurodegenerative diseases. Neuroepithelial stem cells serve as a starting population for the generation of midbrain organoids by contacting them with differentiation medium under agitating conditions in three-dimensional cell culture comprising a matrix.

Abstract: Modulators of TRIM-NHL proteins and their use for modulating the proliferation and differentiation potential of stem cells and progenitor cells. Inhibitors of TRIM-NHL proteins, e.g. TRIM32, are useful for stem cell maintenance in vitro and in vivo. Assay methods for identifying TRIM-NHL protein modulators make use of the E3 ligase activity of TRIM32 or its interaction with Argonaute-1.

Abstract: Modulators of TRIM-NHL proteins and their use for modulating the proliferation and differentiation potential of stem cells and progenitor cells. Inhibitors of TRIM-NHL proteins, e.g. TRIM32, are useful for stem cell maintenance in vitro and in vivo. Assay methods for identifying TRIM-NHL protein modulators make use of the E3 ligase activity of TRIM32 or its interaction with Argonaute-1.