Mots-Clés

single nuclei RNA Sequencing, trophoblast stem cells, Placenta, Preeclampsia, IUGR

Description

Preeclampsia is an hypertensive disorder which complicates 2 to 5% of pregnancies, causes 76 000 maternal deaths each year worldwide and is one of the major causes of extreme prematurity (20% of preterm births before 32 weeks of gestation). There is currently no curative treatment, and only childbirth and delivery of the placenta alleviate the mother’s symptoms. Extremely preterm infants birth management is a major societal challenge in medical, ethical and economic terms. Preeclampsia arises from poor development of the early placenta due to mechanisms still incompletely elucidated, compromising the differentiation of villous and extravillous trophoblast. It is now possible to reprogram somatic cells and pluripotent stem cells into trophoblast stem cells to explore the trophoblast differenciation during interaction with maternal interface, especially the mechanisms triggering and leading to the fate of the human syncytiotrophoblast.

For more information please consult this publication from David’s lab:

Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells.  Castel G, Meistermann D, Bretin B, Firmin J, Blin J, Loubersac S, Bruneau A, Chevolleau S, Kilens S, Chariau C, Gaignerie A, Francheteau Q, Kagawa H, Charpentier E, Flippe L, François-Campion V, Haider S, Dietrich B, Knöfler M, Arima T, Bourdon J, Rivron N, Masson D, Fournier T, Okae H, Fréour T, David L. Cell Rep. 2020 Nov 24;33(8):108419. doi: 10.1016/j.celrep.2020.108419.

This project aims to analyze datasets (Bulk RNAseq, Single Cell RNAseq, Single Nucleus RNAseq) obtained from human trophoblast stem cell cultures and normal/pathological human placentas.

The researcher will interact with other bioinformaticians from Dr. David's team (University of Nantes) and from the Cochin Institute.

The appointment is for 24 months. Starting date is flexible, ideally by December 2023

The objectives are :

- to understand the molecular transcriptomic mechanisms underlying terminal differentiation of villous trophoblast into syncytiotrophoblast after interaction with maternal endometrial cells.

-to understand how the terminal differentiation pathways of the syncytiotrophoblast are altered during preeclampsia, whether or not associated with intra-uterine growth retardation.

 Experience / Skills:

- Training in bioinformatics, statistics, or data science with knowledge and interest in developmental biology

- Experience working in a Unix environment and statistical analysis using R and Python

- Experience with transcriptome data analysis, single-cell data analysis and/or multi/omics integration tools