Wells, C. C. | bioRxiv Science

bioRxiv2026

An interaction between Yorkie and Taiman transcriptional coactivators regulates niche-to-stem cell BMP signaling in the female Drosophila germline

Communication between stem cells and their specialized niche microenvironments is vital for organism development and tissue homeostasis. However, mechanisms that limit intracellular signaling within a given niche and thus maintain stem cell fate are not fully understood. The Hippo and Ecdysone nuclear receptor (EcR) pathways are well conserved and individually required in niche cells for the establishment and maintenance of stem cell pools in Drosophila. These pathways are linked in the nucleus via a physical interaction between their respective transcriptional coactivators Yorkie (Yki) and Taiman (Tai). Within the female Drosophila germline niche, Yki and Tai each regulate behavior of stem cells and their progeny. It is not known whether these roles are mechanistically distinct or are a product of a physical interaction between Yki and Tai that enables a common niche-support role. Here we utilize a CRISPR mutant fly line containing a form of Tai unable to bind Yki (taiPPxA) to examine requirements for the Yki:Tai interaction in vivo. We find that the Yki:Tai interaction controls the GSC niche mainly through a role in escort cells (ECs), a key somatic cell-type that ensheathes the niche and regulates intercellular signaling. taiPPxA reduces EC cytoplasmic processes and allows the Dpp ligand to spread beyond its normally restricted range within the GSC niche, which elevates Dpp signaling and blocks differentiation of GSC progeny. In sum, these findings suggest that a Yki:Tai interaction facilitates crosstalk between the Hippo and EcR pathways within ECs and thus plays a critical role in maintaining intercellular signals that allow somatic cells to shape the niche microenvironment.

cell biology↗

bioRxiv2024

Differentiating Peromyscus leucopus bone marrow-derived macrophages for characterization of responses to Borrelia burgdorferi and lipopolysaccharide

Currently, most tools utilized in host-pathogen interaction studies depend on the use of human or mouse (Mus musculus) cells and tissues. While these species have led to countless breakthroughs in our understanding of infectious disease, there are undoubtably important biological processes that are missed by limiting studies to these two vertebrate species. For instance, it is well-established that a common North American deermouse, Peromyscus leucopus, has unique interactions with microbes, which likely shape its ability to serve as a critical reservoir for numerous zoonotic pathogens, including a Lyme disease spirochete, Borrelia burgdorferi. In this work, we expand the immunological toolkit to study P. leucopus biology by performing the first differentiation of deermouse bone marrow to macrophages using P. leucopus M-CSF producing HEK293T cells. We find that P. leucopus BMDMs generated through this method behave broadly very similarly to C57BL/6J macrophages generated with L-929 supernatant, though RNA sequencing revealed modest differences in transcriptomic responses to B. burgdorferi and lipopolysaccharide. In particular, differences in Il10 induction and caspase expression were observed between the species.

immunology↗