Biology subjects

Acosta-Iborra, B.

Publications and source records attributed to Acosta-Iborra, B..

3 recordsLinked to original sources

bioRxiv2025

Transcriptomic profile of embryoid bodies under hypoxia at single cell level

Oxygen availability is a key regulator of cellular physiology and hypoxia plays a central role driving vasculogenesis and angiogenesis during development. While bulk transcriptomics has revealed important oxygen-regulated gene networks, such approaches cannot resolve the cellular heterogeneity and lineage dynamics characteristic of early differentiation. To address this, we generated a single-cell transcriptomic dataset from murine embryoid bodies, a widely used in vitro model of early embryonic development, cultured 8 or 10 days under hypoxic (1% O2) or normoxic (21% O2) conditions for the final 16 or 48 hours of differentiation. This resource enables detailed exploration of how oxygen availability influences lineage specification, vascular and hematopoietic development, and cellular heterogeneity during early differentiation. Beyond developmental biology, the dataset provides a valuable reference for comparative studies of hypoxia responses, benchmarking of single-cell analysis methods, and integrative investigations into oxygen signaling across diverse biological systems.

cell biology↗

bioRxiv2024

Bhlhe40 limits proliferation and prevents excessive angiogenesis in mouse embryoid bodies under hypoxia

Knowledge of the molecular mechanisms that underlie the regulation of the major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functional role of the transcriptional repressor basic-helix-loop-helix family member e40 (Bhlhe40), which we previously identified in a meta-analysis as one of the most consistently up-regulated genes in response to hypoxia across various cell types. We investigated the role of Bhlhe40 in controlling proliferation and angiogenesis using a gene editing strategy in mouse embryonic stem cells (mESCs) that we differentiated in embryoid bodies (EBs). We observed that hypoxia-induced Bhlhe40 expression was compatible with the rapid proliferation of pluripotent mESCs under low oxygen tension. However, in EBs, hypoxia triggered a Bhlhe40-dependent cell cycle arrest in most progenitor cells and endothelial cells within vascular structures. Furthermore, Bhlhe40 knockout increased the basal vascularization of the EBs in normoxia and exacerbated the hypoxia-induced vascularization, supporting a novel role for Bhlhe40 as a negative regulator of blood vessel formation. Our findings implicate Bhlhe40 in mediating key functional adaptive responses to hypoxia, such as proliferation arrest and angiogenesis.

molecular biology↗

bioRxiv2017

The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia

Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output.

genomics↗