Research
▪ 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.
Fates of all individual cells underlie tissue health and disease.
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.
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.
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.
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.
Selected Publications
Wehling, Blood 2022
Kull, Blood 2022
Loeffler, Nature 2019
Loeffler, Blood 2018
Hilsenbeck, Bioinformatics 2017
Buggenthin, Nature Methods 2017
Hilsenbeck, Nature Biotechnology 2016
Skylaki, Nature Biotechnology 2016
Hoppe, Nature 2016
Kokkaliaris, Blood 2016
Filipczyk, Nature Cell Biology 2015
Eilken, Nature 2009
Rieger, Science 2009
Development of custom software has proven crucial for every step of data acquisition, curation and analysis.
Published software can be downloaded here
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.
Published hardware can be downloaded here
We analyze the function and regulation of:
We work in these human and mouse cell systems:
Selected Publications
Wehling, Blood 2022
Kull, Blood 2022
Ahmed, Journal of Experimental Medicine 2022
Loeffler, Blood 2022
Wang, Blood 2021
Kokkaliaris, Blood 2020
Ahmed, Stem Cell Reports 2020
Loeffler, Nature 2019
Etzrodt, Blood 2019
Buggenthin, Nature Methods 2017
Endele, Blood 2017
Hoppe, Nature 2016
Kokkaliaris, Blood 2016
Schroeder, Cell Stem Cell 2010
Eilken, Nature 2009
Kimura, Blood 2009
Rieger, Science 2009
Schroeder, EMBO Journal 2000
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.