Biology subjects

Ortega, N.

Publications and source records attributed to Ortega, N..

3 recordsLinked to original sources

bioRxiv2023

A non-canonical Hippo pathway represses the expression of deltaNp63

The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, the protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in the MCF10A mammary epithelial cell line as well as in squamous and breast cancer cell lines, expression of {Delta}Np63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases in a manner that is independent of p53. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. We additionally identified additional genes that were similarly regulated suggesting the broader importance of this pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased YAP protein levels, thereby constituting a feedback loop. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells. One Sentence SummaryRegulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells

cancer biology↗

bioRxiv2021

Reprogrammed iBlastoids contain amnion-like cells but not trophectoderm

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of embryo models hinges on their molecular, cellular and structural fidelities to their in vivo counterparts. To authenticate human embryo models, single-cell RNA-sequencing has been utilised for unbiased transcriptional profiling. However, a well-organised and integrated human single-cell RNA-sequencing dataset, serving as a universal reference for benchmarking human embryo models, remains unavailable. Herein, we developed such a reference, through integration of six published human datasets covering developmental stages from the zygote to the gastrula. Lineage annotations are contrasted and validated with available human and non-human primate datasets. Using stabilised UMAP we constructed a web tool, where query datasets can be projected on the reference and annotated with predicted cell identities. Using this reference tool, we examined several recent human embryo models, highlighting the risk of misannotation when relevant references are lacking.

developmental biology↗

bioRxiv2018

Impacts of thermal mismatches on chytrid fungus Batrachochytrium dendrobatidis prevalence are moderated by life stage, body size, elevation and latitude

Global climate change is increasing the frequency of unpredictable weather conditions; however, it remains unclear how species-level and geographic factors, including body size and latitude, moderate impacts of unusually warm or cool temperatures on disease. Because larger hosts and lower-latitude hosts generally have slower acclimation times, we hypothesized that their disease susceptibility increases under \"thermal mismatches\", or differences between baseline climate and the temperature during surveying. Here, we examined how thermal mismatches interact with body size, life stage, habitat, latitude, elevation, phylogeny, and IUCN conservation status to predict infection prevalence of the chytrid fungus Batrachochytrium dendrobatidis (Bd) in a global analysis of 38,967 amphibian hosts. As hypothesized, we found that the susceptibility of larger hosts and hosts from lower latitudes was strongly influenced by thermal mismatches. Furthermore, hosts of conservation concern are more susceptible than others following thermal mismatches, suggesting that thermal mismatches might have contributed to recent amphibian declines.\n\nData Accessibility StatementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository such as Dryad or Figshare and the data DOI will be included at the end of the article.

ecology↗