| dc.description.abstract | This dissertation introduces a new research system, Turritopsis dohrnii (Cnidaria, Hydrozoa), that can further our understanding of tissue regeneration, cellular plasticity and aging using a genomic approach. When exposed to physical damage, adverse environmental conditions, or senescence, medusae of T. dohrnii will transform into a cyst stage, which then reverts back to the juvenile polyp. The underlying mechanism that enables its ontogenetic reversal is called cell transdifferentiation (i.e., cell reprogramming), a process in which mature, fully differentiated cells can switch into another needed cell type of any lineage. The following interconnected projects are presented: I) Transcriptome assembly/annotation of T. dohrnii stages involved in reverse development and bioinformatics analysis to identify genes and networks that underlie its transdifferentiation and ontogeny reversal; II) Expression profiling of genetic networks involved in mammalian longevity, regeneration, and pluripotency, such as Sirtuins, Heat-shock Proteins, and POU domain factors, and subsequent gene-tree analyses to investigate the evolutionary history of such factors in T. dohrnii; III) Construct a draft genome for T. dohrnii through generating and assembling genomic reads and subsequent scaffolding of the genome using RNA-sequencing libraries and transcriptome.
Genetic constituents and networks associated to aging/lifespan, transposable element regulation, and response to DNA damage, were identified to be highly active in cyst stage, where cell transdifferentiation occurs. The reversed polyp developed from transdifferentiation processes show marked differences in its transcriptional profile compared to colonial polyps produced from budding, such as heightened activity of genes associated to chromatin remodeling, matrix metalloproteinases, and embryonic development. Furthermore, profiling analyses revealed that T. dohrnii highly regulates genes imperative to the interconnected networks of regeneration, pluripotency, and longevity in mammals during its ontogeny reversal sequence, such as SIRT3, HSP90, and POU factors, and homology-based and phylogenetic analyses support the presence of Yamanaka factor homologs in T. dohrnii, warranting further exploration and advanced orthology analyses. Lastly, the generation of the first draft genome for T. dohrnii has provided insight into the complexity of the assembly of its genome and represents an essential initial step in developing the species as an unparalleled research system to investigate the genetics of cellular plasticity and reprogramming, in vivo. | |
