Biology subjects

Navarrete, E.

Publications and source records attributed to Navarrete, E..

6 recordsLinked to original sources

bioRxiv2026

Stepwise reorganization of chromosome conformation and nuclear organization during stem cell differentiation

Nuclear organization is a fundamental feature of cell identity and cell fate determination. Compared with differentiated cells, pluripotent stem cells exhibit markedly distinct nuclear architecture at multiple levels, including chromosome folding, lamina association, histone modification landscapes and nuclear body organization. Although individual aspects of this reorganization have been characterized, how and in what order these features are remodeled as cells commit to a lineage remains poorly understood. Here, we temporally map nuclear reorganization across five stages of an in vitro differentiation system of human embryonic stem cells through definitive endoderm and hepatoblast intermediates into hepatocyte-like cells. By integrating Hi-C, RNA-seq, ATAC-seq, ChIP-seq, and CUT&RUN data, we establish a genome-wide framework linking structural, epigenetic, and transcriptional changes across differentiation. Combined with immunofluorescence imaging, chromosome painting, and liquid chromatin Hi-C (LC-Hi-C) we show that nuclear reorganization proceeds in a stepwise and temporally ordered manner through three major transitions. In the first transition, chromosomes condense into defined territories concurrent with transient anchoring of centromere-proximal regions to the nuclear periphery. In a second transition, active and inactive chromatin segregate, leading to stronger compartmentalization. This coincides with deposition and peripheralization of H3K9me2-marked chromatin and morphological changes in nuclear speckles, while chromatin conformation at speckle-associated regions stabilizes. In a third transition, after lineage-specific genes are activated, chromatin interactions globally stabilize, establishing a more stable nuclear architecture on top of these earlier large-scale structural rearrangements. Together, our results define a stepwise framework for nuclear reorganization during human embryonic stem cell differentiation and reveal that the transition from pluripotency to a differentiated state proceeds through coordinated, temporally ordered structural events.

genomics↗

bioRxiv2024

Interphase chromosome conformation is specified by distinct folding programs inherited via mitotic chromosomes or through the cytoplasm

Identity-specific interphase chromosome conformation must be re-established each time a cell divides. To understand how interphase folding is inherited, we developed an experimental approach that physically segregates mediators of G1 folding that are intrinsic to mitotic chromosomes from cytoplasmic factors. Proteins essential for nuclear transport, RanGAP1 and Nup93, were degraded in pro-metaphase arrested DLD-1 cells to prevent the establishment of nucleo-cytoplasmic transport during mitotic exit and isolate the decondensing mitotic chromatin of G1 daughter cells from the cytoplasm. Using this approach, we discover a transient folding intermediate entirely driven by chromosome-intrinsic factors. In addition to conventional compartmental segregation, this chromosome-intrinsic folding program leads to prominent genome-scale microcompartmentalization of mitotically bookmarked and cell type-specific cis-regulatory elements. This microcompartment conformation is formed during telophase and subsequently modulated by a second folding program driven by factors inherited through the cytoplasm in G1. This nuclear import-dependent folding program includes cohesin and factors involved in transcription and RNA processing. The combined and inter-dependent action of chromosome-intrinsic and cytoplasmic inherited folding programs determines the interphase chromatin conformation as cells exit mitosis.

genomics↗

bioRxiv2023

Unique territorial and sub-chromosomal organization revealed in the holocentric moth Bombyx mori

Hallmarks of multicellular eukaryotic genome organization are chromosome territories, compartments, and loop-extrusion-mediated structures, including TADs. However, these are mainly observed in model organisms, and most eukaryotes remain unexplored. Using Hi-C in the silkworm Bombyx mori we discover a novel chromatin folding structure, compartment S, which is "secluded" from the rest of the chromosome. This compartment exhibits loop extrusion features and a unique genetic and epigenetic landscape, and it localizes towards the periphery of chromosome territories. While euchromatin and heterochromatin display preferential compartmental contacts, S domains are remarkably devoid of contacts with other regions, including with other S domains. Polymer simulations show that this contact pattern can only be explained by high loop-extrusion activity within compartment S, combined with low extrusion elsewhere through the genome. This unique, targeted extrusion represents a novel phenomenon and underscores how evolutionarily conserved mechanisms--compartmentalization and loop extrusion--can be repurposed to create new 3D genome architectures.

genomics↗

bioRxiv2023

The role of the Frontal Aslant tract in bilingual language control

In the present study, we investigated the microstructural properties of the right and left Frontal Aslant tract (FAT) in relation to bilingualism and language modality by comparing a group of unimodal bilinguals (i.e., bilinguals proficient in two spoken languages) and a group of bimodal bilinguals (i.e., bilinguals proficient in a spoken and a signed language). We found that the microstructural properties of the left FAT were related to the performance in semantic fluency in the second language (L2), either signed or spoken. Additionally, only for bimodal bilinguals, the microstructural properties of the right FAT were related to picture naming performance in the first spoken language (L1). No significant effects on performance were found in a language comprehension task. Overall, the results suggest that the FAT plays a significant role in language production in bilinguals. The left FAT appears to be involved primarily during the use of spoken or signed L2, while the right FAT appears to be involved in handling the competition of the signed L2 language while speaking L1.

neuroscience↗

bioRxiv2020

Commonalities in alpha and beta neural desynchronizations during prediction in language comprehension and production

The present study investigates whether predictions during language comprehension are generated by engaging the production system. We recorded EEG from participants performing both a comprehension and a production task in two separate blocks. Participants listened to high and low constraint incomplete sentences and were asked either to name a picture to complete it (production) or to simply listen to the final word (comprehension). We found that in a silent gap before the final stimulus, predictable stimuli elicited alpha (8-10 Hz) and beta (13-30 Hz) desynchronization in both tasks. Source estimation highlighted not only the involvement of the left-lateralized language network, but also of temporo-parietal areas in the right hemisphere. Furthermore, correlations between the desynchronizations in comprehension and production showed spatiotemporal commonalities in language-relevant areas in the left hemisphere, especially in the temporal, lateral inferior and dorsal frontal, and inferior parietal corteces. As proposed by prediction-by-production models, our results show that comprehenders engage the production system while predicting upcoming words.

neuroscience↗

bioRxiv2018

Italian norms and naming latencies for 357 high quality color images

In the domain of cognitive studies on the lexico-semantic representational system, one of the most important means of ensuring well-suited experimental designs is using ecological stimulus sets accompanied by normative data on the most relevant variables affecting the processing of their items. In the context of image sets, color photographs are particularly suited for this aim as they reduce the difficulty of visual decoding processes that may emerge with traditional image sets of line drawings, especially in clinical populations. We provide Italian norms for a set of 357 high quality image-items belonging to 23 semantic subcategories. Data from several variables affecting image processing: age of acquisition, familiarity, lexical frequency, manipulability, name agreement, typicality and visual complexity; were collected from a sample of 255 Italian-speaking participants. Lexical frequency data were derived from the CoLFIS corpus. Furthermore, we collected data with on image naming latencies aimed at exploring how much of the variance in these latencies could be explained by the above mentioned critical variables. Multiple regression analyses on the naming latencies show classical psycholinguistic phenomena, such as the effects of age of acquisition and name agreement. In addition, manipulability is also a significant predictor. The described Italian normative data and naming latencies are available for download as supplementary material.

animal behavior and cognition↗