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Conservation of primordial ~12-hour ultradian gene programs in humans

ABSTRACT: Conservation of primordial ~12-hour ultradian gene programs in humans

PROVIDER: PRJNA908830 | ENA |

REPOSITORIES: ENA

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Conservation of primordial ~12-hour ultradian gene programs in humans

Project description:Biological rhythms have important implications for human disease, as evidenced by the effects of disrupting the 24h circadian clock. While circadian rhythms are entrained to the once daily light-dark cycle of the sun, coastal marine organisms are known to exhibit 12h ultradian rhythms, corresponding to the twice daily movement of the tides. Human ancestors emerged from a circa-tidal environment millions of years ago. However, whether 12h ultradian rhythms are conserved in humans remains unknown. Here, we performed prospective, high temporal resolution transcriptome profiling in the peripheral white blood cells of three healthy subjects. Remarkably, all three subjects exhibited a shared transcriptional program demonstrating robust ~12h rhythms. Pathway analysis implicated 12h transcriptional oscillations primarily affected core cellular processes, including RNA and protein metabolism, with strong homology to the 12h gene programs previously identified in cnidarian marine species. These results establish the existence of 12h biological rhythms in humans. Such rhythms appear to have a primordial evolutionary origin dating back at least 700 million years and are likely to have far-reaching implications in human health and disease.

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Comparison of human primordial oocyte follicles to ovarian somatic cells

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Conservation and divergence of myelin proteome profiles between humans and mice

Project description:While myelin is commonly assessed in mice as a model for humans, it remained unclear to which extent their myelin protein composition is similar. We analyzed the proteome of myelin biochemically purified from human white matter by two steps of discontinuous sucrose density gradient centrifugation intermitted by osmotic shocks. We utilized a data-independent acquisition (DIA) workflow with alternating low and elevated energy (MSE) and an ion mobility-enhanced version thereof (referred to as UDMSE) to achieve both, a correct quantification of exceptionally abundant myelin proteins and a comprehensive coverage of the myelin proteome. Label-free protein quantification revealed that the relative abundance of the structural myelin proteins PLP, MBP, CNP and SEPTIN8 correlates well with that in c57Bl/6N-mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. Species-dependent diversity of myelin protein composition can be instructive when translating from mouse models to humans.

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Tracing the emergence of primordial germ cells from bilaminar disc rabbit embryos and pluripotent stem cells (cell culture)

Project description:Rabbit embryos, as in humans, develop as bilaminar discs at gastrulation and unlike egg cylinders as in rodents. Mammalian primordial germ cells (PGCs) in all species originate during gastrulation. We sequence the transcriptomes of rabbit embryos during gastrulation, and show that rabbit PGC (rbPGC) specification occurs at the posterior epiblast at the onset of gastrulation

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Robust induction of primordial germ cells of white rhinoceros on the brink of extinction

Project description:In vitro gametogenesis, the process of generating gametes from pluripotent cells in culture, is a powerful tool for improving our understanding of germ cell development as well as an alternative source of gametes.(1) Conservation of the northern white rhinoceros (NWR), a species for which only two females remain, would be a compelling application of in vitro gametogenesis as a gametes source. Here, we established a culture system that induces a robust number of primordial germ cell-like cells (PGCLCs) from pluripotent stem cells of the NWR and southern white rhinoceros (SWR), the closest species to the NWR. PGCLC differentiation from SWR embryonic stem cells is highly reliant on BMP and WNT signals, as observed in mice and humans, though the timing and duration of these signals need to be optimized for each species. Genetic analysis revealed that SOX17 is essential for SWR-PGCLC induction, as it is in humans. Under the defined condition, NWR induced pluripotent stem cells differentiated into PGCLCs whose transcriptome was highly similar to that of SWR-PGCLCs. We also identified cell surface markers, CD9 and ITGA6, that enabled us to isolate PGCLCs without genetic alteration in pluripotent stem cells. This study provides a first step toward production of NWR gametes in culture and understanding of the basic mechanism of PGC specification in a large animal.

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