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Content archived on 2024-06-18

Origin and lineage specification of trophoblast cells in early human placenta

Objective

My central question: how does the human placenta develop and how are specialized trophoblast sub-types generated? Despite advances in placental biology, pregnancy disorders occur frequently with few treatment options available, resulting in considerable maternal and/or infant mortality and morbidity. The cause of these disorders is abnormal early placental development but ethically and practically this is hard to investigate. Developing in vitro models that are truly representative of normal first trimester trophoblast will allow investigation of lineage specification and differentiation. I will take an interdisciplinary approach to characterize the first trimester villous cytotrophoblast (VCT) population. Specifically, I aim to:
1. Characterize the expression of trophoblast stem (TS) cell transcription factors and epigenetically regulated genes to identify the anatomical compartment(s) containing population(s) with stem cell characteristics
2. Isolate VCT using a specific cell surface marker and perform an in-depth molecular characterization at a single cell level to identify putative TS cells
3. Characterize cell signalling pathways in the VCT and in the putative TS cell population
4. Establish cell culture conditions for TS cells
5. Perform a detailed characterization of cells cultured in vitro
This proposal has arisen from preliminary results obtained working in Centre for Trophoblast Research, University of Cambridge. Working in a lab with extensive experience of trophoblast isolation (Prof. A.Moffett) and input from our collaborators, Dr. M.Hemberger and Prof. G.Burton who have experience in mouse TS cells and human placental function in vivo, respectively has been pivotal. I am thus in an ideal position to capitalize on this expertise together with other stem cell labs in Cambridge to develop essential tools and knowledge to understand early developmental processes during placentation. It also has important translational impact for women and their babies.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2013-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
EU contribution
€ 231 283,20
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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