The Bageritz lab deconstructs the heterogeneity of muscle stem cell niches during development to understand how stem cell number and cellular identity are built and regulated, and their impact on adult muscle biology with the ultimate goal of promoting healthy aging. To address this, we apply modern approaches such as AI-assisted microscopy image analysis, cell type-specific CRISPR gene editing, single-cell RNA sequencing, and spatial transcriptomics to dissect key principles and their underlying mechanisms at cellular resolution.
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 temporally defined manner, complemented by a variety of single-cell transcriptomic methods to study the dynamic muscle stem/cell niche interaction in a living organism. Shared principles are then tested with the help of our collaborators in vertebrate systems. This integrative approach allows us to uncover conserved mechanisms that govern stem cell behavior across species, advancing our understanding of muscle biology and stem cell niches.
We currently pursue the following scientific directions and research priorities:
1. Pool Size Regulation of Muscle Stem/Progenitor Cells During Development
With a focus on the role of Wnt signaling as a key regulator of developmental muscle stem cell pool size, we aim to understand how signaling specificity is achieved within one stem cell niche that harbors different muscle stem/progenitor populations. Cell-type-specific and spatially-restricted expression and function of pathway components, together with integration of signaling pathway cross-talk, will reveal basic principles in context-dependent pool size building mechanisms. Our research seeks to elucidate how these pathways are fine-tuned to maintain a balance between stem cell proliferation and differentiation.
2. Developmentally Derived MuSC Pool Impact on Adult Muscle Biology
By investigating how the muscle stem cell (MuSC) pool established during development influences adult muscle function, we aim to uncover the long-term effects of early-life stem cell dynamics. Understanding these relationships will provide insights into how developmental processes shape adult tissue homeostasis and regenerative capacity, potentially leading to strategies for improving muscle function and health during aging.
3. Tools for Advanced Spatial Analysis
We develop two sets of spatial tools to address the complexity of muscle stem cell niches. The first set focuses on unbiased transcriptome profiling of small cells, utilizing both computational and experimental approaches. This will help us derive candidate genes relevant for MuSC pool size regulation. The second set of tools involves AI-assisted microscopy for the quantitative assessment of the muscle stem/progenitor pool sizes and their heterogeneous cellular features, allowing us to study functional consequences of gene perturbations at high spatial resolution enabling unprecedented insights into the cellular dynamics of muscle stem cell niches.
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