Biology subjects

Bloomer, H.

Publications and source records attributed to Bloomer, H..

4 recordsLinked to original sources

bioRxiv2025

Triple-Negative Breast Cancer Cells Activate Sensory Neurons via TRPV1 to Drive Nerve Outgrowth and Tumor Progression

The tumor microenvironment in triple-negative breast cancer (TNBC) is characterized by increased sensory nerve density, which contributes to cancer progression by promoting migration and metastasis. However, the origin of tumor-innervating nerves and the mechanisms driving sensory innervation into tumors remain poorly understood. Using in vivo retrograde labeling techniques, we show that mammary tumors are associated with an increase in nerves originating from the dorsal root ganglia. Additionally, we find that TNBC cells trigger stress and activation markers and induce neuronal firing in a transient receptor potential anilloid subtype 1 (TRPV1)-dependent manner. In both 2D and 3D cell culture models, TNBC cells promote outgrowth of sensory nerves that is abrogated with Trpv1 knockout. We identified c-Jun and IL-6 as an effector of neurite outgrowth that acts downstream of TRPV1 to promote outgrowth in vitro. Finally, in Trpv1 knockout mice, TNBC tumors exhibit delayed growth and reduced lung metastasis. These findings suggest that a critical role for TRPV1 in tumor-nerve crosstalk, offering a potential target to reduce metastatic disease.

cancer biology↗

bioRxiv2025

ZUGC-RNA degradation generates immunosuppressor to evade immune responses in eukaryotes

Among the hundreds of modified nucleosides identified in terrestrial life, 2-amino-6-aminopurine (Z) is widely recognized as a prominent modified purine. Recently, RNA written with the ZUGC alphabet shows significant potential in RNA therapeutics as a synthetic biosystem. Here, we demonstrate that ZUGC-RNA can evade immune recognition in eukaryotes, independent of factors such as RNA length, sequence, 5-triphosphate, modified uridine, and secondary structure. Notably, we discovered that both the degradation of ZUGC-RNA and metabolites of Z-nucleotides can function as immunosuppressors, silencing TLR7 sensing to block immune responses. This mechanism differs from that of pseudo-uridine ({Psi}) modified RNA currently in use. ZUGC-RNAs also demonstrate broad applicability across multiple neural cell types. Our findings provide valuable insights for developing more tolerable RNA-based drugs and designing immunomodulators targeting TLR7. In addition to the potential prebiotic relevance of Z, our finding not only contributes to understanding the RNA world hypothesis but also provides new insights into the exploration of the origin of life.

synthetic biology↗

bioRxiv2023

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

BackgroundMetastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis. MethodsWe evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell lines cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines. ResultsWe identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo. ConclusionsOur results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.

cancer biology↗

bioRxiv2019

Robust generation of erythroid and multilineage hematopoietic progenitors from human iPSCs using a scalable monolayer culture system

One of the most promising objectives of clinical hematology is to derive engraftable autologous hematopoietic stem cells (HSCs) from human induced pluripotent stem cells (iPSCs). Progress in translating iPSC technologies to the clinic relies on the availability of scalable differentiation methodologies. In this study, human iPSCs were differentiated for 21 days using STEMdiff, a monolayer-based approach for hematopoietic differentiation of human iPSCs that requires no replating, co-culture or embryoid body formation. Both monolayer and suspension cells were functionally characterized throughout differentiation. In the supernatant fraction, an early transient population of primitive CD235a+ erythroid cells first emerged, followed by hematopoietic progenitors with multilineage differentiation activity in vitro but no long-term engraftment potential in vivo. In later stages of differentiation, a nearly exclusive production of definitive erythroid progenitors was observed. In the adherent monolayer, we identified a prevalent population of mesenchymal stromal cells and limited arterial vascular endothelium (VE), suggesting that the cellular constitution of the monolayer may be inadequate to support the generation of HSCs with durable repopulating potential. Quantitative modulation of WNT/{beta}-catenin and activin/nodal/TGF{beta} signaling pathways with CHIR/SB molecules during differentiation enhanced formation of arterial VE, definitive multilineage and erythroid progenitors, but was insufficient to orchestrate the generation of engrafting HSCs. Overall, STEMdiff provides a clinically-relevant and readily adaptable platform for the generation of erythroid and multilineage hematopoietic progenitors from human pluripotent stem cells.\n\nHighlightsO_LIRobust, scalable and clinically-relevant monolayer-based culture system for hematopoietic differentiation of human iPSCs.\nC_LIO_LISuccessive emergence of primitive erythroid cells, definitive multilineage HSPCs and erythroid progenitors in the culture supernatant.\nC_LIO_LIAbundant mesenchymal cells and limited arterial vascular endothelium in the culture monolayer.\nC_LIO_LICHIR/SB molecules increase arterial vascular endothelium formation, suppress primitive hematopoiesis and promote definitive multilineage and erythroid progenitors.\nC_LI

developmental biology↗