Biology subjects

Fernandez-Minan, A.

Publications and source records attributed to Fernandez-Minan, A..

5 recordsLinked to original sources

bioRxiv2026

Single-cell multiomics identifies key nodes and cis-regulatory elements of the networks specifying the eye domains in zebrafish

Congenital eye malformations result from disruptions in the early developmental programs that specify and regionalize the eye primordium. Human genetics and developmental studies in animal models have identified critical regulatory nodes within the gene regulatory networks (GRNs) patterning the distinct eye domains. However, the fundamental cis-regulatory connectivity of these networks, and their dynamic behaviour, remains poorly understood. To address these gaps, we performed a comprehensive analysis of transcriptome dynamics and chromatin accessibility at single-cell resolution in the developing zebrafish forebrain. Our single-cell multiomic approach enabled us to characterize the regulatory landscape of the main eye derivatives: neural retina, optic stalk, pigmented epithelium and lens; alongside adjacent diencephalic and telencephalic regions. We identified and functionally validated tissue-specific cis-regulatory modules, and predicted highly connected nodes within each domain. Notably, we uncovered the role of foxp1b as a conserved central node within the neural retina network, highlighting the predictive power of our analysis in reconstructing the architecture of the GRNs that specify the vertebrate eye. TeaserIdentification of central nodes and cis-regulatory networks involved in eye patterning by single-cell multiomics in zebrafish.

developmental biology↗

bioRxiv2025

Neotenic transcriptomic features in the adult turquoise killifish brain

Aging is one of the main challenges facing modern society. Understanding the cellular processes that occur in the later stages of life is essential to address age-related diseases. Although aging is a global process that affects the entire body, the brain is one of the most sensitive organs and is affected by numerous degenerative diseases. In this study, we investigate cell types and genes that are particularly sensitive to the aging process. To this end, we performed a time-course single-cell RNAseq experiment series in the brain of the killifish, the vertebrate model with the shortest lifespan, which makes it an excellent model for aging studies. Our analysis reveals that non-glial progenitor cells are among those populations that change the most between young and old animals. Furthermore, we identify specialized stromal clusters that seem to support a primitive hematopoietic program in the brain, which is active only during the embryonic stages in other vertebrate species. Our results show that the expression of embryonic genes in the adult brain appears to be a general feature in killifish, and that several cell populations in the adult killifish brain show a higher level of similarity to the zebrafish embryonic populations than to adult ones. Our study suggests that adult killifish maintain a neotenic gene expression status in the brain that may help in sustaining their characteristic high proliferation and metabolic rates, as well as combat the detrimental effects of this high metabolism on cells, especially at advanced ages.

genomics↗

bioRxiv2023

The cellular landscape of the endochondral bone highlights its multipotent and immunomodulatory features during the transition to extrauterine life

The cellular complexity of the endochondral bone underlies its essential and pleiotropic roles during organismal life. While the adult bone has received significant attention, we still lack a deep understanding of the perinatal bone cellulome. Here, we have profiled the full composition of the murine endochondral bone at the single-cell level during the transition from fetal to newborn life and in comparison to the adult tissue, with particular emphasis on the mesenchymal compartment. The perinatal bone contains different fibroblastic clusters with blastema-like characteristics in organizing and supporting skeletogenesis, angiogenesis, and hematopoiesis. Our data also suggests dynamic inter- and intra-compartment interactions as well as a bone marrow milieu that seems prone to anti-inflammation, which we hypothesize is necessary to ensure the proper program of lymphopoiesis and the establishment of central and peripheral tolerance in early life. Our study provides an integrative roadmap for the future design of genetic and cellular functional assays to validate cellular interactions and lineage relationships within the perinatal bone.

cell biology↗

bioRxiv2021

Trap-TRAP, a versatile tool for tissue-specific translatomics in zebrafish

Developmental and physiological processes depend on the transcriptional and translational activity of heterogeneous cell populations. A main challenge in gene expression studies is dealing with this intrinsic complexity while keeping sequencing efficiency. Translating ribosome affinity purification (TRAP) methods have allowed cell-specific recovery of polyribosome-associated RNAs by genetic tagging of ribosomes in selected cell populations. Here we combined the TRAP approach with adapted enhancer trap methods (trap-TRAP) to systematically generate zebrafish transgenic lines suitable for tissue-specific translatome interrogation. Through the random integration of the eGFP:rpl10a cassette, we have generated stable lines driving expression in a variety of tissues, including the retina, skeletal muscle, lateral line primordia, rhombomeres, or jaws. To increase the range of applications, a UAS:TRAP transgenic line compatible with available Gal4 lines was also generated and tested. The resulting collection of lines and applications constitutes a resource for the zebrafish community in developmental genetics, organ physiology and disease modelling.

developmental biology↗

bioRxiv2020

Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression

Control of gene expression is dictated by cell-type specific regulatory sequences that physically organize the structure of chromatin, including promoters, enhancers and insulators. While promoters and enhancers convey cell-type specific activating signals, insulators prevent the cross-talk of regulatory elements within adjacent loci and safeguard the specificity of action of promoters and enhancers towards their targets in a tissue specific manner. Using the mouse tyrosinase (Tyr) locus as an experimental model, a gene whose mutations are associated with albinism, we described the chromatin structure in cells at two distinct transcriptional states. Guided by chromatin structure, through the use of Chromosome Conformation Capture (3C), we identified sequences at the 5 and 3 boundaries of this mammalian gene that function as enhancers and insulators. By CRISPR/Cas9-mediated chromosomal deletion, we dissected the functions of these two regulatory elements in vivo in the mouse, at the endogenous chromosomal context, and proved their role as genomic insulators, shielding the Tyr locus from the expression patterns of adjacent genes.

genomics↗