Publications by authors named "M Schuelke"
Thyroid hormone receptor alpha (THR) is a nuclear hormone receptor that binds triiodothyronine (T3) and acts as an important transcription factor in development, metabolism, and reproduction. The coding gene, , has two major splicing isoforms in mammals, and , which encode THR1 and THR1, respectively. The better characterized isoform, THR1, is a transcriptional stimulator of genes involved in cell metabolism and growth.
View Article and Find Full Text PDFT cell immune tolerance is established in part through the activity of the Auto-immune Regulator (AIRE) transcription factor in the medullary Thymic Epithelial Cells (mTEC) of the thymus. AIRE induces expression of SELF peripheral tissue-specific antigens for presentation to naïve T cells to promote activation/deletion of potentially autoreactive T cells. We show, for the first time to our knowledge, that tumors mimic the role of AIRE in mTEC to evade immune rejection.
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- Leigh syndrome (LS) is a severe mitochondrial disease caused by mutations in over 100 genes that impair cellular respiration and mainly affect brain function, leading to cognitive and motor issues.
- Various model systems, including yeast, fruit flies, zebrafish, and mice, have been developed over 30 years to study the disease's mechanisms and symptoms.
- Recent advancements in using induced pluripotent stem cells (iPSCs) enable researchers to examine LS mutations in human cells, facilitating high-throughput drug screening and the potential for personalized treatments.
Article Synopsis
- Thyroid hormone receptor alpha (THRα) is a crucial receptor that binds T3 and regulates important biological processes such as development, metabolism, and reproduction through its two main isoforms, THRα1 and THRα2.
- THRα1 promotes gene expression for cell metabolism and growth, while THRα2, which lacks the ligand-binding capability, is thought to inhibit the function of THRα1, making their ratio essential for proper gene regulation.
- The study utilized RNA-sequencing methods to analyze expression patterns of these isoforms in healthy human tissues and the developing brain, revealing a significant prevalence of THRα1 during various stages of brain development and in adult central nervous system tissues.
Article Synopsis
- Human-derived experimental systems like induced pluripotent stem cells (iPSCs) help researchers understand mitochondrial disorders and develop treatments.
- Two iPSC lines were created from patient fibroblasts with different mutations in the MT-ATP6 gene, leading to distinct mitochondrial diseases: NARP syndrome and Maternally Inherited Leigh Syndrome.
- The process of reprogramming used Sendai virus to introduce factors that maintain the cells' pluripotency, and the mutation levels (heteroplasmy) remained stable after this process.