Biology subjects

Ledesma-Terron, M.

Publications and source records attributed to Ledesma-Terron, M..

5 recordsLinked to original sources

bioRxiv2026

NucLogic: Logic-based geometric 3D nuclear segmentation for fast and robust analysis of challenging biological imaging data

Nuclear segmentation in 3D microscopy remains challenging, particularly for low signal-to-noise ratio (SNR) data from timelapse imaging, in vivo experiments, or dense tissue samples. Yet accurate 3D nuclear segmentation is a prerequisite for quantitative single-cell analysis, making this a key bottleneck for high-throughput study of challenging datasets. We present NucLogic, a fast and robust 3D nuclear segmentation algorithm that combines the maturity of 2D segmentation with geometric stitching rules based on nuclear shape, orientation, and intensity, to reconstruct accurate 3D volumes. NucLogic reliably segments challenging datasets including long-term timelapse imaging of organoids, and large dense structures such as the zebrafish brain. Benchmarked against other state-of-the-art segmentation tools, NucLogic matches F1 scores at high SNR, with increasing outperformance as SNR decreases. Importantly, segmentation completes at 20-50% of the computation time, with greater speed gains on larger images. Beyond segmentation, NucLogic includes an intuitive graphical user interface allowing non-experts to segment, quantify, and visualize 3D and 4D data. This enables easy quantification of cell numbers and integration of a variety of both cell-intrinsic properties, such as phenotype, morphology, and local environment metrics, including density and spatial interactions. Together, NucLogic makes quantitative 3D nuclear analysis of previously unmanageable datasets accessible to a broad research community.

cell biology↗

bioRxiv2024

High-throughput three-dimensional characterization of morphogenetic signals during the formation of the vertebrate retina

The balance between self-renewal and terminal differentiation of neural progenitors is regulated by a complex interplay of signaling pathways that set the spatial and temporal cues that ultimately shape and organize neurogenic tissues. In this contribution, we combine in toto experiments with three-dimensional image analysis, computational modeling, and theoretical tools to provide a quantitative characterization of the dynamics of growth and differentiation of the developing vertebrate retina. We show that the tissue develops by gradually increasing the average rate of differentiation and reducing the average cell cycle length. Moreover, this balance between differentiation and cell cycle duration increases the yield of production of terminally differentiated neurons, and it is required to achieve a well-defined exponential growth. We also show that a potential regulator of this balance is Hedgehog (Hh), promoting simultaneously cell cycle progression and cell cycle exit of RPCs. Our results represent a detailed and accurate quantitative characterization of retinal neurogenesis and how signals regulate the balance between proliferation and differentiation during the development of the vertebrate retina.

systems biology↗

bioRxiv2023

Cell competition promotes metastatic intestinal cancer through a multistage process

Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids and microtissues to explore the impact of cell competition on liver metastasis. Unlike competition at the primary site, the initial effect on liver progenitor cells does not involve the induction of apoptosis. Instead, metastatic competition manifests as a multistage process. Initially, liver progenitors undergo compaction, which is followed by cell cycle arrest, ultimately forcing differentiation. Subsequently, the newly differentiated liver cells exhibit reduced cellular fitness, rendering them more susceptible to outcompetion by intestinal cancer cells. Notably, cancer cells leverage different interactions with different epithelial populations in the liver, using them as scaffolds to facilitate their growth. Consequently, tissue-specific mechanisms of cell competition are fundamental in driving metastatic intestinal cancer.

cancer biology↗

bioRxiv2020

Stretching of the retinal pigment epithelium contributes to zebrafish optic cup morphogenesis

The vertebrate eye primordium consists of a pseudostratified neuroepithelium, the optic vesicle (OV), in which cells acquire neural retina or retinal pigment epithelium (RPE) fates. As these fates arise, the OV assumes a cup-shape, influenced by mechanical forces generated within the neural retina. Whether the RPE passively adapts to retinal changes or actively contributes to OV morphogenesis remains unexplored. Here, we generated a zebrafish Tg(E1-bhlhe40:GFP) line to track RPE morphogenesis and interrogate its participation in OV folding. We show that, in virtual absence of proliferation, RPE cells stretch into a squamous configuration, thereby matching the curvature of the underlying retina. Forced proliferation and localized interference with the RPE cytoskeleton disrupt its stretching and OV folding. Thus, extreme RPE flattening and accelerated differentiation are efficient solutions adopted by fast-developing species to enable timely optic cup formation. This mechanism differs in amniotes, in which proliferation largely drives RPE expansion with a much-reduced need of cell flattening.

developmental biology↗

bioRxiv2019

Radial Glial from mammalian developing neocortex can divide symmetrically in vitro

Radial Glial progenitors in the mammalian developing neocortex have been shown to follow a deterministic differentiation program restricted to an asymmetric-only mode of division. This feature seems incompatible with their well known ability to expand in number when cultured in vitro, driven by Fibroblast Growth Factor 2 and other mitogenic signals. The changes in their differentiation dynamics that allow this transition from in vivo asymmetric-only division mode to an in vitro self-renewing culture have not been fully characterized. Here we combine experiments of Radial Glia cultures with theory and numerical models to show that Fibroblast Growth Factor 2 has a triple effect by simultaneously increasing the growth fraction, promoting symmetric divisions and shortening the length of the cell cycle. This combined effect of Fibroblast Growth Factor 2 in the differentiation dynamics of Radial Glial progenitors partner to establish and sustain a pool of rapidly proliferating in vitro pool of Radial Glial progenitors.

developmental biology↗