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Diez-Pinel, G.

Publications and source records attributed to Diez-Pinel, G..

3 recordsLinked to original sources

Novel markers for haemogenic endothelium and haematopoietic progenitors in the mouse yolk sac

Erythro-myeloid progenitors (EMPs) originate from the haemogenic endothelium in the yolk sac via an endothelial-to-haematopoietic transition (EHT) to generate blood and immune cells that support embryo development. Yet, the transitory nature of EHT and the limited availability of molecular markers has constrained our understanding of the origin, identity and differentiation dynamics of EMPs. Here, we have refined the annotation of yolk sac haemato-vascular populations in publicly available single-cell RNA sequencing (scRNAseq) datasets from mouse embryos to identify novel molecular markers of haemogenic endothelium and EMPs. By sub-clustering key cell populations followed by pseudotime analysis, we refined cluster annotations and then reconstructed differentiation trajectories. Subsequent differential gene expression analysis between clusters identified novel cell surface markers for haemogenic endothelial cells (Fxyd5 and Scarf1) and EMPs (Fcer1g, Tyrobp and Mctp1). Further, we have identified candidate signalling and metabolic pathways that may regulate yolk sac haematopoietic emergence and differentiation. The specificity of FXYD5, SCARF1 and FCER1G for haemogenic endothelium and EMPs was validated by immunostaining of mouse yolk sac. These insights into the transcriptional dynamics in the yolk sac should support future investigation of EHT and haematopoietic differentiation during early mammalian development.

developmental biology↗

A Pax3 lineage gives rise to transient haematopoietic progenitors

During embryonic development, muscle tissues, skin, and a subset of vascular endothelial cells arise from Pax3-expressing embryonic progenitors defined as paraxial mesoderm. By contrast, haemogenic potential is well established for extra-embryonic mesoderm and intra-embryonic lateral plate mesoderm which do not express Pax3. To date, it is not known whether the haematopoietic system also contains Pax3 lineage cells. Here, we show that the mouse foetal liver and foetal circulation contain a transient population of Pax3 lineage cells with hallmarks of haematopoietic progenitors and the potential to generate both myeloid and erythroid cells. We propose that Pax3 lineage haematopoietic cells should be investigated to better understand normal haematopoietic development from different mesodermal derivatives. Further, genetic alterations of Pax3 lineage haematopoietic cells should be investigated for their potential to cause haematopoietic malignancies.

developmental biology↗

BulkECexplorer: a bulk RNAseq compendium of five endothelial subtypes that predicts whether genes are active or leaky

Transcriptomic data obtained by single cell (sc) RNAseq or bulk RNAseq can be mined to understand the molecular activity of cell types. Yet, lowly expressed but functional genes may remain undetected in RNAseq experiments for technical reasons, such as insufficient read depth or gene drop out in scRNAseq assays. By contrast, bulk RNAseq assays may detect lowly expressed mRNA transcripts thought to be the biologically irrelevant products of leaky transcription. To more accurately represent a cells functional transcriptome, we propose compiling many bulk RNAseq datasets into a compendium and applying established classification models to predict whether the detected genes are likely active or leaky in that cell type. Here, we have created such a compendium for vascular endothelial cells from several mouse and human organs, termed the BulkECexplorer.

bioinformatics↗