Stem cell niches are dynamic microenvironments that control stem cell behaviour during development and adult life of an organism. These complex cell-to-cell interactions play an important role in functional organ development as well as adult tissue repair. We study the crosstalk between muscle stem cells and their niches to understand how stem cell reservoirs are built during development, maintained in adulthood and replenished during aging and age-related diseases.
We use the fruit fly Drosophila melanogaster as an in vivo model system to understand basic principles in cell-cell communication. Specific cell-types or even individual cells can be labeled and manipulated in a temporal defined manner and complemented by a variety of single-cell transcriptome methods to study the dynamic muscle stem/cell niche interaction in a living organism.
One focus of the lab is on the role of Wnt signaling as a key regulator of these processes. For instance, in the developing epithelial wing imaginal disc of Drosophila, which acts as a stem cell niche for the adjacent adult muscle stem/progenitor cells (AMPs), the Drosophila Wnt1 homolog Wingless (Wg) plays an important role for AMP specification and proliferation. However, its role on different muscle stem/progenitor cell populations within one tissue is so far not understood and will be part of a newly founded project of the SFB1324. We will combine our findings with studies done in the male germline stem cell niche in the group of Ingrid Lohmann to unravel a context- dependent and also generalizable Wnt input and output code influenced by cross-talk with other signaling pathways at cellular resolution.
To better understand and ultimately modulate tissue regeneration and the process of aging, we want to dissect cellular heterogeneity in muscle tissue and identify factors that control muscle stem cell number and cell cycle exit. To identify genes with functional relevance, we use single-cell transcriptomic methods and our previously developed bioinformatic tools to compute and analyze expression maps (Bageritz et al., 2019) together with in vivo CRISPR/Cas-based genetic screening.
Another focus of the lab is on tool development to directly link cellular features and single-cell transcriptomics. Biophysical characteristics and molecular features, such as cellular size, cell cycle speed/exit, and cellular polarity, are analyzed to resolve heterogeneity in muscle stem cell pool sizes. For this, we modify standard dropseq-based technologies, which then allow a sequencing-based readout, combine live cell imaging and single-cell RNA sequencing (scRNAseq), and develop computational tool to infer cellular features from scRNAseq data.
Our Collaborations
Sergio Acebrón, Heidelberg University
Eileen Furlong, EMBL
Florian Heigwer, Bingen Technical University of Applied Sciences
Thomas W. Holstein – Heidelberg University
Jan Philipp Junker, MDC Berlin
Ingrid Lohmann, Heidelberg University
Moritz Mall, DKFZ
Julia von Maltzahn, BTU Cottbus-Senftenberg