Biology subjects

Varley, A.

Publications and source records attributed to Varley, A..

3 recordsLinked to original sources

bioRxiv2025

An unexpected mode of whole-body regeneration from reaggregated cell suspension in Hydractinia (Cnidaria, Hydrozoa)

Hydrozoan cnidarians are among the few animals that can regenerate whole bodies from reaggregated cell dissociations but the cellular and molecular mechanisms that control this ability and how it is related to embryonic development are not well understood. Furthermore, the evolution of this type of regeneration is enigmatic since it does not occur naturally. Here, we show that aggregate regeneration in Hydractinia symbiolongicarpus proceeds through several, consistent stages that include the formation of an epidermal layer, followed by migration, proliferation, and differentiation of adult pluripotent stem cells, known as i-cells. Migration of i-cells is controlled by sphingosine-1-phosphate signaling. Single-cell transcriptomics revealed, surprisingly, that the newly regenerated individual derives nearly exclusively from i-cell progeny rather than from recycled somatic cells, as seen in other hydrozoans. Given the similarity of this phenomenon to embryogenesis, we propose that the ability of Hydractinia cell aggregates to regenerate is a side effect of the animals i-cell-mediated development.

developmental biology↗

bioRxiv2023

AGILE Platform: A Deep Learning-Powered Approach to Accelerate LNP Development for mRNA Delivery

Ionizable lipid nanoparticles (LNPs) have seen widespread use in mRNA delivery for clinical applications, notably in SARS-CoV-2 mRNA vaccines. Despite their successful use, expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored to different target cell types. The traditional process of LNP development remains labor-intensive and cost-inefficient, relying heavily on trial and error. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines the iterative development of ionizable lipids, crucial components for LNP-mediated mRNA delivery. This approach brings forth three significant features: efficient design and synthesis of combinatorial lipid libraries, comprehensive in silico lipid screening employing deep neural networks, and adaptability to diverse cell lines. Using AGILE, we were able to rapidly design, synthesize, and evaluate new ionizable lipids for mRNA delivery in muscle and immune cells, selecting from a library of over 10,000 candidates. Importantly, AGILE has revealed cell-specific preferences for ionizable lipids, indicating the need for different tail lengths and head groups for optimal delivery to varying cell types. These results underscore the potential of AGILE in expediting the development of customized LNPs. This could significantly contribute to addressing the complex needs of mRNA delivery in clinical practice, thereby broadening the scope and efficacy of mRNA therapies. One Sentence SummaryAI and combinatorial chemistry expedite ionizable lipid creation for mRNA delivery.

biochemistry↗

bioRxiv2022

Pluripotent, germ cell competent adult stem cells underlie cnidarian plant-like life history

In most animals, pluripotency is irreversibly lost post-gastrulation. By this stage, all embryonic cells have already committed either to one of the somatic lineages (ectoderm, endoderm, mesoderm) or to the germline. The lack of pluripotent cells in adult life may be linked to organismal aging. Cnidarians (corals, and jellyfish) are an early branch of animals that do not succumb to age, but the developmental potential of their adult stem cells remains unclear. Here, we show that adult stem cells in the cnidarian Hydractinia symbiolongicarpus (known as i-cells) are pluripotent. We transplanted single i-cells from transgenic fluorescent donors to wild type recipients and followed them in vivo in the translucent animals. Single engrafted i-cells self-renewed and contributed to all somatic lineages and to gamete production, co-existing with and eventually displacing the allogeneic recipients cells. Hence, a fully functional, sexually competent individual can originate from a single adult i-cell. Given that some of their cells remain pluripotent beyond embryogenesis and throughout life, we conclude that Hydractinia embryos never complete gastrulation. Pluripotent i-cells underlie a regenerative, plant-like life history in these animals.

developmental biology↗