▪ Molecular control of (stem) cell fate decisions ▪ Continuous long-term single-cell quantification ▪ Blood, pluripotent, bone and cancer (stem) cells
Many organs like blood, skin and intestine have the amazing capability for life-long regeneration and repair. Every second of our life, millions of the right type of cells have to be produced in these tissues at the right time and place.
(Schroeder)
Fates of all individual cells underlie tissue health and disease.
(Schroeder)
We analyze how these cell fates are controlled at the molecular level.
This will allow manipulation of cell behavior for clinical therapy. Due to their huge therapeutic potential in regenerative medicine, stem and progenitor cells are of particular interest.
Although usually ignored, the ability to quantify cell fate decisions and molecular dynamics continuously and at the single cell level is a crucial prerequisite when trying to understand molecular cell fate control.
Snapshot analyses with data from only few time points usually allow too many different interpretations about underlying mechanisms. This is the reason for many long standing scientific disputes.
Selected Reviews Kull, Journal of Experimental Medicine2021 Loeffler, Blood 2019 Skylaki, Nature Biotechnology 2016 Etzrodt, Cell Stem Cell 2014 Hoppe, Nature Cell Biology 2014 Schroeder, Nature Methods 2011 Schroeder, Nature 2008 Schroeder, Annals - New York Academy of Science 2005
For a better understanding of the cellular and molecular dynamics underlying health and disease, we therefore develop bioimaging approaches to allow the long-term quantification of cellular and molecular behavior of all individual cells in cell cultures for up to several weeks.
Tracked ESC colony. (Hastreiter, Hilsenbeck, Schroeder, and Skylaki et al., Nature Biotechnology 2016)
We combine - (stem) cell purification and culture - molecular manipulation - microscopic imaging - software development for image acquisition and analysis - engineering of experimental hardware to enable the documentation and analysis of cell fate decisions and their molecular control with improved resolution.
Live single-cell Nanog quantification in ESC colony over several days. (modified from Filipczyk et al., Nature Cell Biology 2015 and Hilsenbeck et al., Nature Biotechnology 2016.)
This combination of novel tools from different disciplines now allows much improved identification of the exact role of cell-intrinsic molecules, signals from the microenvironment and synthetic compounds on (stem) cell behavior.
We design and produce custom hardware for improved laboratory experimentation, culture, manipulation and retrieval of cells and imaging. Products include microfluidic chips, larger 3D-printed devices, small robots and electronics - all including their required control software.
Selected Publications Dettinger, BioRx2021 / Nature Communications 2022 Dettinger, Lab on a Chip 2020 Dettinger, Analytical Chemistry 2018
We analyze the function and regulation of:
(modified from from Krumsiek et al, PLoS One 2011)
Transcription factors and their networks control cell fates. We therefore develop approaches to manipulate and quantify components, topology, wiring and dynamics of transcription factor networks - ideally live in single cells.
We analyze the influence of signaling pathways and their networks in directing cell fate choices through transcription factors by quantitative long-term live single-cell bioimaging.
Continuous single cell quantification is crucial for the analysis of asymmetric cell division. We analyze its role and regulation in hematopoietic and pluripotent stem and progenitor cells.
Selected Publications Wehling, Blood 2022 Loeffler, Blood 2022 Loeffler, Current Opinion in Hematology 2021 Loeffler, Nature 2019 Loeffler, Annals - New York Academy of Science 2019 Schroeder, Cell Stem Cell 2007
Selected Publications Filipczyk et al., Nature Cell Biology 2015 Filipczyk et al., Cell Stem Cell 2013 Warlich et al., Mol Ther 2011 Eilken et al., Nature 2009 Schroeder et al., Mech Dev 2006 Schroeder et al., PNAS 2003
(Coutu, Kokkaliaris, Kunz)
Skeletal or mesenchymal stem cells show great promise for therapy but their biology remains poorly understood. To better characterize these cells, and their role as a niche for other cell types in the bone marrow, we are using novel approaches for multidimensional FACS analyses, lineage tracing approaches and multicolor confocal whole bone imaging.
Selected Publications Kokkaliaris et al., Blood 2020 Kunz et al., Cell Stem Cell 2019 Bourgine et al., PNAS 2018 Bourgine et al., Cell Stem Cell 2018 Coutu et al., Nature Methods 2018 Coutu et al., Nature Biotechnology 2017
