Biology subjects

Goncalves, L. E. D.

Publications and source records attributed to Goncalves, L. E. D..

2 recordsLinked to original sources

bioRxiv2026

A neuroimmune IL-13 axis is associated with human enteric nervous system development

The mechanisms governing maturation of the human enteric nervous system (ENS) during early postnatal life remain poorly defined. Here, we characterize the transcriptomic, cellular, and functional landscape of the neonatal human ileum and identify a neuro-immune axis associated with ENS expansion. Using human tissue transcriptomics, flow cytometry, iPSC-derived enteric neural lineages, and single-cell interactome analyses, we show that the neonatal ileum is enriched for pro-neurogenic transcriptional programs and harbors a greater abundance of enteric neurons and glia than the adult tissue. T cells emerge as a predominant source of interleukin-13 (IL-13) in the neonatal gut, and enteric neurons express its receptor IL13RA1, enabling direct immune-to-neuron signaling. Functional experiments demonstrate that IL-13 enhances expression of key enteric neuronal markers in a concentration-dependent manner. In parallel, single-cell analyses identify enteric neurons as a major predicted source of macrophage migration inhibitory factor (MIF), with signaling directed toward T and NK cell populations, suggesting that the ENS actively shapes the immune environment it depends upon. Together, these findings support a model in which bidirectional neuro-immune communication establishes a pro-neurogenic niche during a critical window of ENS development. This work positions the neonatal immune system as an active contributor to ENS maturation and offers a new perspective on how neuro-immune crosstalk shapes intestinal development in early life.

neuroscience↗

bioRxiv2026

DRP1-mediated mitochondrial fission integrates growth hormone signaling with metabolic and stress adaptation in triple-negative breast cancer

Triple-negative breast cancer (TNBC) relies on metabolic plasticity to sustain growth under diverse microenvironmental conditions. Although growth hormone (GH) signaling has been linked to breast cancer progression, its mechanistic integration with mitochondrial dynamics and metabolic reprogramming remains unclear. Here, we show that GH promotes TNBC progression accompanied by DRP1-associated mitochondrial remodeling, as indicated by sensitivity to Mdivi-1. The MDA-MB-231 line enabled integrated assessment across 2D, 3D, hypoxia, and in vivo xenografts using consistent workflows and readouts. GH increased proliferation and mitochondrial mass without increasing OCR under protein normalization. Instead, GH selectively enhanced glycolytic flux and metabolic flexibility. Inhibition of DRP1 uncoupled GH-induced glycolysis from proliferation, demonstrating that mitochondrial fission is required to link metabolic reprogramming to cell-cycle progression. DRP1 inhibition with Mdivi-1 was associated with altered TP53 and HIF1A expression and extended GH activity to the regulation of a pro-inflammatory tumor microenvironment marked by cxcr4b, il8, and il12. Consistent with these findings, analysis of human TNBC transcriptomes revealed conserved enrichment of mitochondrial, metabolic, and inflammatory pathways. Together, these results support the GH-DRP1 axis as a candidate regulator of mitochondrial dynamics, metabolic plasticity, tumor progression and tumor microenvironment interactions in TNBC.

cancer biology↗