Jameson, V. | Search bioRxiv

bioRxiv2026

Starship transposons mobilise via a circular intermediate with potential biotechnological applications

Mobile genetic elements drive genome evolution and horizontal gene transfer, yet the mechanisms underlying the mobility of many eukaryotic elements remain poorly understood. Here we show that Starships, a recently discovered class of giant transposable elements in fungi, mobilise via an extrachromosomal circular intermediate. Using deep sequencing, we detect low-abundance reads spanning the hypothesised junction consistent with circularisation. We demonstrate that a synthetic circular intermediate, or "starmid", is sufficient for recombinase-dependent integration into the host genome and that circularisation enhances expression of the starship-encoded tyrosine recombinase through juxtaposition of 3' and 5' terminal sequences. This topology-dependent regulation parallels bacterial integrative elements, in which excision activates recombination machinery. Exploiting this circular intermediate, we explore starmids as a platform for transient DNA delivery, enabling CRISPR Cas9-mediated genome editing in Paecilomyces variotii with subsequent curing of the construct. Together, our results shed light on the biology of starship mobility and suggest promising biotechnology applications for these elements.

molecular biology↗

bioRxiv2024

Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors

Dendritic cells (DCs) are rare innate immune cells that are essential regulators of anti-tumour, anti-viral and vaccine responses by the adaptive immune system. Conventional dendritic cells, particularly the cDC1 subset, are most desired for DC-based immunotherapies, however, it can be difficult to isolate sufficient numbers of primary cells from patients. The most common alternate sources of DC are ex vivo, such as monocyte-derived or DC expanded from cord blood hematopoietic progenitors. Induced pluripotent stem cells (iPSC) offer a promising solution, providing an opportunity for in vitro generating DCs that are suitable for patient-derived or off-the-shelf batch-manufactured cells. Here, we developed an in vitro protocol designed to maximise the yield of iPSC-derived DC progenitors, with the specific goal of generating DC1-like cells. The iPSC-DCs subsets generated by our method could be partitioned by cell surface phenotypes of cDC1, cDC2 and DC3, but they were most transcriptionally similar to monocyte-derived DC (MoDC). Stimulated iPSC-DCs generated pro-inflammatory cytokines, expressed migratory chemokine receptors including CCR7 which indicates capacity to traffic through lymphatic endothelium, and upregulated co-stimulatory molecules, indicating their potential for productive interactions with T-cells. This method offers a promising step towards an expandable source of allogeneic human dendritic cells for future applications.

cell biology↗