Biology subjects

Gomis, R.

Publications and source records attributed to Gomis, R..

3 recordsLinked to original sources

bioRxiv2026

Integrated molecular and functional profiling identifies E0771 as a basal-like triple-negative breast cancer model

Breast cancer is a heterogeneous disease whose clinical management relies heavily on accurate molecular subtyping. The murine E0771 mammary carcinoma cell line is widely used in preclinical studies, yet its molecular identity remains controversial, with reports variably classifying it as luminal B or triple-negative. In this study, we performed an integrated molecular and functional characterization of two independently sourced E0771 cell line stocks to resolve this discrepancy. Both stocks were genetically authenticated and exhibited concordant phenotypes. Immunohistochemical and molecular analyses demonstrated absence of oestrogen and progesterone receptors, classifying E0771 as triple-negative. Functionally, E0771 cells showed no transcriptional response to oestrogen and displayed resistance to endocrine therapy both in vitro and in vivo. Collectively, our results establish E0771 as an oestrogen-independent, basal-like triple-negative breast cancer model, supporting its appropriate use in studies of hormone-resistant breast cancer biology.

cancer biology↗

bioRxiv2026

Sodium tungstate promotes vascularization to support beta bell replacement in diabetes

Insufficient vascularization remains a major obstacle to the success of cell-based therapies for diabetes. Building on prior findings that loss of the phosphatase PTP1B enhances VEGFA production and improves graft vascularization, we investigated sodium tungstate (NaW), a pharmacological phosphatase inhibitor, as a strategy to improve transplantation outcomes. Using human fibroblast-derived insulin-producing cells and human stem cell-derived islets transplanted into the anterior chamber of the eye in immunodeficient mice, we show that NaW treatment significantly increases both vascularized area and insulin-positive tissue area, while reducing apoptosis within transplanted cells. Mechanistically, NaW upregulates VEGFA expression in transplanted cells and amplifies VEGFA-induced endothelial cell proliferation, migration, and tubulogenesis via MAPK/ERK signalling. These dual effects, which encompass stimulating both endocrine and endothelial compartments, lead to enhanced integration and function of transplanted cells. Importantly, the pro-angiogenic effects of NaW occur independently of exogenous endothelial cell supplementation, relying solely on the hosts endogenous endothelial cells. These findings position NaW, and potentially other phosphatase inhibitors, as promising adjuncts to improve vascularization, survival, and therapeutic efficacy in clinical cell-based transplantation protocols for diabetes. One-sentence summaryProangiogenic role of sodium tungstate in transplantation

physiology↗

bioRxiv2021

Direct reprogramming of human fibroblasts into insulin-producing cells by transcription factors

Direct lineage reprogramming of one somatic cell into another bypassing an intermediate pluripotent state has emerged as an alternative to embryonic or induced pluripotent stem cell differentiation to generate clinically relevant cell types. One cell type of clinical interest is the pancreatic {beta} cell that secretes insulin and whose loss and/or dysfunction leads to diabetes. Generation of functional {beta}-like cells from developmentally related somatic cell types (pancreas, liver, gut) has been achieved via enforced expression of defined sets of transcription factors. However, clinical applicability of these findings is challenging because the starting cell types are not easily obtainable. Skin fibroblasts are accessible and easily manipulated cells that could be a better option, but available studies indicate that their competence to give rise to {beta} cells through similar direct reprogramming approaches is limited. Here, using human skin fibroblasts and a protocol that ensures high and consistent expression of adenovirus-encoded reprogramming factors, we show that the transcription factor cocktail consisting of Pdx1, Ngn3, MafA, Pax4 and Nkx2-2 activates key {beta} cell genes and down-regulates the fibroblast transcriptional program. The converted cells produce insulin and exhibit intracellular calcium responses to glucose and/or membrane depolarization. Furthermore, they secrete insulin in response to glucose in vitro and after transplantation in vivo. These findings demonstrate that transcription factor-mediated direct reprogramming of human fibroblasts is a feasible strategy to generate insulin-producing cells.

developmental biology↗