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Pare, L.

Publications and source records attributed to Pare, L..

2 recordsLinked to original sources

Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii

Background: Restorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regeneration in this major group remains a key goal. Among annelids, the nereididae Platynereis dumerilii (re)emerged recently as a front-line regeneration model. Following amputation of its posterior part, Platynereis worms can regenerate both differentiated tissues of their terminal part as well as a growth zone that contains putative stem cells. While this regeneration process follows specific and reproducible stages that have been well characterized, the transcriptomic landscape of these stages remains to be uncovered. Results: We generated a high quality de novo Reference transcriptome for the annelid Platynereis dumerilii. To do so, we produced and analyzed three RNA-sequencing datasets, encompassing five stages of posterior regeneration, along with blastema stages and non-amputated tissues as controls. We included these regeneration RNA-seq datasets, as well as embryonic and tissue-specific datasets from the literature to produce a Reference transcriptome. We used this Reference transcriptome to perform in depth analyzes of RNA-seq data during the course of regeneration to reveal the important dynamics of the gene expression, process with thousands of genes differentially expressed between stages, as well as unique and specific genes expression at each regeneration stage. The study of these genes highlighted the importance of the nervous system at both early and late stages of regeneration, as well as the enrichment of RNA-binding proteins (RBPs) during almost the entire regeneration process. Conclusions: In this study, we provided a high-quality de novo Reference transcriptome for the annelid Platynereis that is useful for investigating various developmental processes, including regeneration. Our extensive stage-specific transcriptional analysis during the course of posterior regeneration shed light upon major molecular mechanisms and pathways, and will foster many specific studies in the future.

genomics↗

In situ single-cell analysis of canonical breast cancer biomarkers: phenotypic heterogeneity and implications on response to HER2 targeting agents.

Breast cancer is a heterogeneous disease. Tumor cells and the surrounding microenvironment form an ecosystem that determine disease progression and response to therapy. To characterize the breast cancer ecosystem and the changes induced by targeted treatment selective pressure, we analyzed 136 HER2-positive tumor samples for the expression of canonical BC tumor diagnostic proteins at a single cell level without disrupting the spatial context. The combined expression of HER2, ER, PR, and Ki67 in more than a million cells was evaluated using a tumor-centric panel combining the four biomarkers in a single tissue section by sequential immunohistochemistry to derive 16 tumor cell phenotypes. Spatial interactions between individual tumor cells and cytotoxic T cells were studied to determine the immune characteristics of the ecosystem and the impact on response to treatment. HER2-positive tumors displayed individuality in tumor cells and immune cells composition, including intrinsic phenotype dominance which only partially overlapped with molecular intrinsic subtyping determined by PAM50 analysis. This single cell analysis of canonical BC biomarkers deepens our understanding of the complex biology of HER2-positive BC and suggests that individual cell-based patient classification may facilitate identification of optimal responders or resistant individual to HER2-targeted therapies.

pathology↗