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研究领域

Investigating the molecular mechanisms underlying stem cell longevity Understanding the molecular mechanisms that underlie stem cell function is critical both for treatment of the degenerative effects caused by aging and for the future of regenerative medicine. Strikingly, animals of non-bilaterian phyla (e.g. cnidarians, ctenophores, sponges) have tissues with high plasticity, experience continual self-renewal, exhibit robust regenerative capabilities, and sometimes lack senescence; this is accomplished using a basic molecular toolkit that vertebrates possess. It is therefore instructive to study the underlying molecular mechanisms of stem cell function in these animals to better understand how we might harness this remarkable power. The so-called germline gene set is actually more broadly expressed in somatic stem cells and other proliferative cell types, particularly in the ancient animal phyla, but the functional significance of this is not understood. Given that the germline is the immortal link to the next generation, it is an intriguing possibility that this gene set contributes to stem cell longevity and plasticity in highly regenerative and long-lived animals. A large number of genes associated with the germ line are now known to be integral members of the PIWI-piRNA pathway (e.g. vasa, tudor family genes, and piwi family genes). This small RNA regulatory pathway is largely germ cell- and stem cell-specific and is distinct from the ubiquitous microRNA pathway. At its center are the PIWI proteins, which bind small RNAs called piwi-interacting RNAs (piRNAs, 26-31 nucleotides in length). It is well established that the PIWI-piRNA complexes repress transposons in the germ line. However, increasing evidence suggests that the pathway also regulates non-transposon targets, likely both in the germ line and in somatic stem cells. Given that small RNA regulatory pathways have the potential to regulate a large number of genes, the PIWI-piRNA pathway is likely a critical component of somatic stem cell function in at least some regenerative, long-lived animals; yet we understand nothing of its function in this regard. My research aims to uncover new somatic functions of the PIWI-piRNA pathway that may impact stem cell longevity using the cnidarian Hydra as a model.

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Siebert and Juliano CE (2017). Sex, Polyps, and Medusae: Determination and maintenance of sex in cnidarians. Mol Reprod Dev. 84(2):105-119 Fresques T, Swartz SZ, Juliano C, Morino Y, Kikuchi M, Akasaka K, Wada H, Yajima M, and Wessel G (2016). The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification. Evol Dev. 18:4, 267-78. PMCID: PMC4943673 Juliano CE and Hobmayer B (2016). Meeting report on "Animal Evolution: New Perspectives From Early Emerging Metazoans", Tutzing, September 14-17, 2015. Bioessays Online Version January 22. Juliano CE, Lin H, and Steele RE (2014). Generation of Transgenic Hydra by Embryo Microinjection. J. Vis. Exp. (91) https://www.jove.com/video/51888/generation-of-transgenic-hydra-by-embryo-microinjection. Juliano CE, Reich A, Liu N, Götzfried J, Zhong M, Uman S, Reenan RA, Wessel GM, Steele RE, and Lin H (2014). PIWI Proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. PNAS 111(1):337-342. PMCID: PMC3890812 Mani SR and Juliano CE (2013). Untangling the web: the diverse functions of the PIWI/piRNA pathway. Mol Reprod Dev. 80(8):632-664. Song JL, Stoeckius M, Maaskola J, Friedländer M, Stepicheva N, Juliano C, Lebedeva S, Thompson W, Rajewsky N, Wessel GM (2012). Select microRNAs are essential for early development in the sea urchin. Dev. Biol. 362(1):104-113. PMCID: PMC3254792 Juliano C*, Wang J*, and Lin H (2011). Uniting germline and stem cells: The function of Piwi proteins and the piRNA pathway in diverse organisms. Annu Rev Genet. 45:447-469. (*Co-first authors). PMCID: PMC3832951 Gustafson EA, Yajima M, Juliano CE, and Wessel GM (2011). Post-translational regulation by gustavus contributes to selective Vasa protein accumulation in multipotent cells during embryogenesis. Dev Biol. 349:440-450. PMCID: PMC3053044 Juliano CE, Swartz SZ, and Wessel GM (2010). A conserved germline multipotency program. Development. 137(24):4113-4126. PMCID: PMC2990204 Juliano C and Wessel GM (2010). Versatile germline genes. Science. 329(5992):640-641. PMCID: PMC3088100 Juliano CE, Yajima M, and Wessel GM (2010). Nanos is required to maintain multipotency in the small micromere lineage of the sea urchin embryo. Dev Biol. 337(2):220-232. PMCID: PMC2812692 Juliano CE, and Wessel GM (2009). An evolutionary transition of vasa regulation in echinoderms. Evolution and Development 11:5, 560-573. PMCID: PMC3034130 Voronina, E., Lopez, M., Juliano, C.E., Gustafson, E., Song, J.L., Extavour, C., George, S., Oliveri, P., McClay, D., Wessel., G.M. (2008). Vasa protein expression is restricted to the small micromeres of the sea urchin, but is inducible in other lineages early in development. Dev Biol. 314:276-286. PMCID: PMC2692673 Juliano CE, Voronina E, Stack C, Aldrich M, Cameron AR, Wessel GM. (2006). Germ line determinants are not localized early in sea urchin development, but do accumulate in the small micromere lineage. Dev Biol. 300:406-415.

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