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O’Neill, A. C., Uzbas, F., Antognolli, G., Merino, F., Draganova, K., Jäck, A., Zhang, S., Pedini, G., Schessner, J. P., Cramer, K., Schepers, A., Metzger, F., Esgleas, M., Smialowski, P., Guerrini, R., Falk, S., Feederle, R., Freytag, S., Wang, Z., Bahlo, M. O’Neill, A. C., Uzbas, F., Antognolli, G., Merino, F., Draganova, K., Jäck, A., Zhang, S., Pedini, G., Schessner, J. P., Cramer, K., Schepers, A., Metzger, F., Esgleas, M., Smialowski, P., Guerrini, R., Falk, S., Feederle, R., Freytag, S., Wang, Z., Bahlo, M., Jungmann, R., Bagni, C., Borner, G. H. H., Robertson, S. P., Hauck, S. M., & Götz, M. (2022). Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity. Science, 376(6599): eabf9088. doi:10.1126/science.abf9088.
Abstract
The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, cell migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at the centrosome of human induced pluripotent stem cell–derived neural stem cells (NSCs) and neurons. Centrosome-associated proteins were largely cell type–specific, with protein hubs involved in RNA dynamics. Analysis of neurodevelopmental disease cohorts identified a significant overrepresentation of NSC centrosome proteins with variants in patients with periventricular heterotopia (PH). Expressing the PH-associated mutant pre-mRNA-processing factor 6 (PRPF6) reproduced the periventricular misplacement in the developing mouse brain, highlighting missplicing of transcripts of a microtubule-associated kinase with centrosomal location as essential for the phenotype. Collectively, cell type–specific centrosome interactomes explain how genetic variants in ubiquitous proteins may convey brain-specific phenotypes. -
Uzbas, F., May, I. D., Parisi, A. M., Thompson, S. K., Kaya, A., Perkins, A. D., & Memili, E. (2015). Molecular Physiognomies and Applications of Adipose-Derived Stem Cells. Stem Cell Reviews and Reports, 11, 298-308. doi:10.1007/s12015-014-9578-0.
Abstract
Adipose-derived stromal/stem cells (ASC) are multipotent with abilities to differentiate into multiple lineages including connective tissue and neural cells. Despite unlimited opportunity and needs for human and veterinary regenerative medicine, applications of adipose-derived stromal/stem cells are at present very limited. Furthermore, the fundamental biological factors regulating stemness in ASC and their stable differentiation into other tissue cells are not fully understood. The objective of this review was to provide an update on the current knowledge of the nature and isolation, molecular and epigenetic determinants of the potency, and applications of adipose-derived stromal/stem cells, as well as challenges and future directions. The first quarter of the review focuses on the nature of ASC, namely their definition, origin, isolation and sorting methods and multilineage differentiation potential, often with a comparison to mesenchymal stem cells of bone marrow. Due to the indisputable role of epigenetic regulation on cell identities, epigenetic modifications (DNA methylation, chromatin remodeling and microRNAs) are described broadly in stem cells but with a focus on ASC. The final sections provide insights into the current and potential applications of ASC in human and veterinary regenerative medicine.
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