Biology subjects

Tellez, N.

Publications and source records attributed to Tellez, N..

3 recordsLinked to original sources

bioRxiv2026

Combinatorial MAPK states drive opposing gene programmes: a reanalysis of MAP3K-driven transcriptional responses in MCF10A cells

BackgroundThe MAPK signalling network coordinates opposing cell fates -- proliferation versus apoptosis -- by combining the activities of ERK, JNK, and p38 kinases in patterns that depend on upstream MAP3K identity. Using multiplexed kinase translocation reporter (KTR) biosensors and functional assays in MCF10A mammary epithelial cells, Peterson et al. (Cell Systems, 2023) demonstrated that MAP3Ks co-activating ERK and JNK drive approximately tenfold more cell cycle entry than MAP3Ks activating ERK alone, and that both kinase activities are independently required for this proliferative response. The transcriptional mechanism underlying this quantitative difference was not identified in the original study. ResultsWe performed a systematic computational re-analysis of the RNA-seq data deposited by Peterson et al. (GEO: GSE213882), encompassing thirteen MAP3K perturbations in doxycycline-induced MCF10A mammary epithelial cells. Based on signalling responses reported by Peterson et al., MAP3Ks were grouped into ERK-only (RAF1, COT) or ERK+JNK co-activating kinases (MLK1, MLK3, ZAK, TAK1, MEKK2, MEKK3). This stratification identified JNK co-activation as the feature most strongly associated with E2F/MYC transcriptional polarity. ERK-only MAP3Ks showed negative enrichment of E2F TARGETS, G2M CHECKPOINT, and MYC TARGETS Hallmark gene sets, whereas ERK+JNK MAP3Ks showed positive enrichment (each MAP3K individually FDR < 0.05 by GSEA). Consistently, inferred activities of E2F1, E2F2, E2F4, and MYC shifted from negative mean ULM t-scores in the ERK group to strongly positive values in the ERK+JNK group (FDR < 0.05 using the CollecTRI regulon). The observed E2F/MYC polarity was robust to alternative transcription factor inference strategies, being reproduced using the DoRothEA A+B regulon and the multivariate model (MLM) framework (Pearson r = 0.77). The signal remained stable under leave-one-out sensitivity analysis and was independently reproduced in MAP3K overexpression signatures from the LINCS L1000 atlas (GEO: GSE92742). ConclusionsERK activation alone was associated with repression of E2F/MYC transcriptional programmes, whereas JNK co-activation was associated with their activation. These opposing transcriptional states provide a potential explanation for the [~]10-fold differences in cell cycle entry reported by Peterson et al. and supports a model in which pRb/E2F regulation integrates combinatorial MAPK co-activation states beyond the canonical ERK-cyclin D-CDK4/6 axis.

genomics↗

bioRxiv2025

Temporal patterns of dominance in a hummingbird assemblage

A substantial gap in dominance hierarchies research is understanding how such relationships change over time. Previous studies have generally used a single interaction matrix, assuming that dominance is temporally consistent. Yet food sources can be scarce and temporary, leading to changes in species frequency and assemblage composition. Hummingbird assemblages fluctuate as these tiny birds track seasonal floral resources, with individual movements affecting species composition. Artificial feeders, which may foster a greater number of aggressive interactions, provide a stable environment for studying dominance, unlike ephemeral and shifting wild resources. To assess the temporal stability of dominance relationships, we documented aggressive interactions in a hummingbird assemblage over three months on the western slope of the eastern Cordillera of Colombian Andes. We tracked local changes in species composition and visit frequency, recording interactions among 11 hummingbird species using high-speed cameras at three time scales: hour, day, and month. Dominance relationships and their certainty were analyzed through Perc analyses and interaction networks. Over three months of recording, and perusing over 27 hours of non continuous highspeed videos, we registered 3,907 aggressive interactions and 12,629 visits. Our results revealed substantial temporal variation in dominance relationships, species composition, and visit frequency, even within the constant food source that feeders provide. Dominance hierarchies were generally intransitive, with large species dominating, but also with smaller species occasionally winning interactions. We found high uncertainty in dominance relationships within shorter intervals with fewer interactions (e.g., hourly); and that rank changes between dominant species across months and days were linked to shifts in feeder visits. We recommend that future studies incorporate temporal variation, certainty analyses, and interaction networks to determine whether dominance relationships are stable enough to form reliable hierarchies and to explore the ecological significance of reversals in dominance and associated determinants. HighlightsO_LIDominance fluctuates across temporal scales, with monthly, daily, and hourly variations. C_LIO_LIHierarchies become less stable at finer temporal scales. C_LIO_LIBody size and feeder visitation frequency shape dominance interactions. C_LIO_LISmaller species initiate more aggressive interactions but lose more frequently. C_LIO_LIRelationships among dominant species are less predictable than among subordinates. C_LI

animal behavior and cognition↗

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↗