@phdthesis{Leer2023,
  author    = {Leer, Marina},
  title     = {Computational analysis of the effects of ageing and diet on stem cell function and ectopic fat accumulation in the musculoskeletal system},
  school      = {Universit{\"a}t Potsdam},
  pages     = {130},
  year      = {2023},
  abstract  = {The musculoskeletal system provides support and enables movement to the body, and its deterioration is a crucial aspect of age-related functional decline. Mesenchymal stromal cells (MSCs) play an important role in musculoskeletal homeostasis due to their broad differentiation potentials and their ability to support osteogenic and myogenic tissue maintenance and regeneration. In the bone, MSCs differentiate either into osteochondrogenic progenitors to form osteocytes and chondrocytes, or increasingly with age into adipogenic progenitors which give rise to bone-resident adipocytes. In skeletal muscle, during healthy regeneration MSCs provide regulatory signals that activate local, tissue-specific stem cells, known as satellite cells, which regenerate contractile myofibres. This process involves a significant cross-talk to immune cells stemming from both lymphoid and myeloid lineages. During ageing, muscle-resident MSCs undergo increased adipogenic lineage commitment, causing niche changes that contribute to fatty infiltration in muscles. These shifts in cell populations in bone lead to the loss of osteogenic cells and subsequently osteoporosis, or in muscle to impaired regeneration and to the development of sarcopenia. However, the signals that drive transition of MSCs into their respective cellular fates remain elusive. This thesis aims to elucidate the transcriptional shifts modulating cell states and cell types in musculoskeletal MSC fate determination. Single-cell RNA-sequencing (scRNA-seq) was used to characterise cell type-specific transcript regulation. State-of-the-art bioinformatics tools were combined with different analytical platforms that include both droplet-based scRNA-seq for large heterogeneous populations, and microfluidics-based scRNA-seq to assess small, rare subpopulations. For each platform, distinct computational pipelines were established including filtering steps to exclude low-quality cells, and data visualisation was performed by dimensionality reduction. Downstream analysis included clustering, cell type annotation, and differential gene expression to investigate transcriptional states in defined cell types during ageing and injury in the muscle and bone. Finally, a novel tool to assess publication activities in defined areas of research for the identified marker genes was developed. The results in the bone indicate that ageing MSCs increasingly commit towards an adipogenic fate at the expense of osteogenic specialisation. The data also suggests that significant cell population shifts of MSC-type fibro-adipogenic progenitors during muscle ageing underlie the pathologies observed in homeostatic and post-injury regenerative conditions. High-throughput visualisation of publication activity for candidate genes enabled more effective biological evaluation of scRNA-seq data. These results expose critical age-related changes in the stem cell niches of skeletal muscle and bone, highlight their respective sensitivity to nutrition and pathology, and elucidate novel factors that modulate stem cell-based regeneration. Targeting these processes might improve musculoskeletal health in the context of ageing and prevent the negative effects of pathological lineage determination.},
  language  = {en}
}
@article{SandmannGarzMenzel2016,
  author    = {Sandmann, Michael and Garz, Andreas and Menzel, Ralf},
  title     = {Physiological response of two different Chlamydomonas reinhardtii strains to light-dark rhythms},
  series = {Botany},
  volume    = {94},
  journal   = {Botany},
  publisher = {NRC Research Press},
  address   = {Ottawa},
  issn      = {1916-2790},
  doi       = {10.1139/cjb-2015-0144},
  pages     = {53 -- 64},
  year      = {2016},
  abstract  = {Cells of a cell-wall deficient line (cw15-type) of Chlamydomonas reinhardtii and of the corresponding wild type were grown during repetitive light-dark cycles. In a direct comparison, both lines showed approximately the same relative biomass increase during light phase but the cw-line produced significantly more, and smaller, daughter cells. Throughout the light period the average cellular starch content, the cellular chlorophyll content, the cellular rate of dark respiration, and the cellular rate of photosynthesis of the cw-line was lower. Despite this, several non-cell volume related parameters like the development of starch content per cell volume were clearly different over time between the strains. Additionally, the chlorophyll-based photosynthesis rates were 2-fold higher in the mutant than in the wild-type cells, and the ratio of chlorophyll a to chlorophyll b as well as the light-saturation index were also consistently higher in the mutant cells. Differences in the starch content were also confirmed by single cell analyses using a sensitive SHG-based microscopy approach. In summary, the cw15-type mutant deviates from its genetic background in the entire cell physiology. Both lines should be used in further studies in comparative systems biology with focus on the detailed relation between cell volume increase, photosynthesis, starch metabolism, and daughter cell productivity.},
  language  = {en}
}