Biology subjects

Saiz, N.

Publications and source records attributed to Saiz, N..

4 recordsLinked to original sources

bioRxiv2026

ZATELLITE: a toolkit to visualize and manipulate human centromeres in live cells using synthetic zinc fingers

Changes in the number of chromosomes or their spatial organization within the nucleus have critical consequences for cell fate. Yet capturing the karyotype or three-dimensional architecture of chromatin in living cells remains limited by the difficulty in labeling endogenous loci non-invasively. The most widely used tools rely on dCas9, a bulky protein whose persistent DNA binding interferes with DNA and RNA metabolism, causes DNA damage, and is hard to multiplex. We developed ZATELLITE, an AI-enabled tool to target endogenous repetitive sequences with fluorescently-tagged synthetic zinc fingers. ZATELLITE probes have key advantages over dCas9: they are smaller, easier to multiplex and, critically, they do not cause DNA damage or chromosomal abnormalities, even after long-term labeling. We generated a collection of ZATELLITE probes to label the centromeres of nearly all human chromosomes, enabling the capture of genome organization and karyotype alterations in real time in living cells. Finally, we show that ZATELLITE can be used for simultaneous labeling and epigenetic editing of centromeres. Thus, ZATELLITE is a non-toxic, versatile tool for genome visualization and manipulation.

cell biology↗

bioRxiv2025

BeadBuddy: user-friendly, nanometer-scale registration of single-molecule imaging data

Single-molecule localization microscopy (SMLM) captures nanoscale detail with fluorescence imaging. As large-area cameras and multiplex imaging become standard, chromatic errors are growing more complex, challenging precise analysis. To address this challenge, we present BeadBuddy, an open-source, user-friendly software that uses images of fluorescent beads to model and correct 3D, spatially varying chromatic errors. BeadBuddy achieves sub-voxel resolution in DNA Fluorescence In Situ Hybridization (FISH) and is applicable across SMLM modalities.

biophysics↗

bioRxiv2019

Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

Precise control and maintenance of the size of cell populations is fundamental for organismal development and homeostasis. The three cell types that comprise the mammalian blastocyst-stage embryo are generated in precise proportions and over a short time, suggesting a size control mechanism ensures a reproducible outcome. Guided by experimental observations, we developed a minimal mathematical model that shows growth factor signaling is sufficient to guarantee this robustness. The model anticipates, without additional parameter fitting, the response of the embryo to perturbations in its lineage composition. We experimentally added lineage-restricted cells to the epiblast both in vivo and in silico, which resulted in a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biased the specification of progenitors towards the targeted cell type. Finally, we show that FGF4 couples cell fate decisions to lineage composition through changes in local concentration of the growth factor. Our results provide a basis for the regulative abilities of the mammalian embryo and reveal how, in a self-organizing system, individual cell fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.

developmental biology↗

bioRxiv2018

Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

To comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio-temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.

developmental biology↗