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Dr Margherita Yayoi Turco

Dr Margherita Yayoi Turco

Group Leader

Royal Society Dorothy Hodgkin Research Fellow


Research Interests

Stem Cell Biology of the Maternal-Fetal interface

Disorders of pregnancy result in considerable maternal and infant mortality and children who survive complicated pregnancies are likely to be faced with life-long developmental challenges. The underlying primary cause of pre-eclampsia, together with fetal growth restriction and stillbirth, collectively termed the Great Obstetric Syndromes (GOS), is abnormal development of the placenta. The placenta is formed by the fetus and is responsible for its nourishment and protection. Despite significant advances in obstetrics and placental biology over the last few years, there are few treatment options available. Thus, there is a great need to unravel the cellular and molecular mechanisms underlying the first stages of placental development to understand what goes awry in pregnancy complications.

The development of the placenta is intimately associated with the endometrium, the lining of the uterus. Proper endometrial growth and differentiation is crucial for a successful pregnancy as there must be an efficient dialogue between these two organs which together constitute the maternal (endometrium) - fetal (placenta) interface. How can we identify and distinguish between the placental and maternal defects that contribute to pregnancy disorders? Studying this has been challenging due to the lack of physiologically relevant in vitro models of human endometrium and placenta.

We have recently developed 3D culture systems (organoids) of human endometrium and placenta which show remarkable phenotypical and functional similarities to their tissue of origin. These organoids can be expanded and cultured long term and contain both stem cells and differentiated cells. Using these 3D culture systems, our lab aims to unravel the basic biological processes underlying the proliferation and differentiation of these two organs. Using an interdisciplinary approach involving 3D culture techniques, single cell RNA sequencing, Crispr/Cas9 genome editing and tissue engineering, we aim to address these three key research questions:

  1. How are the specialized trophoblast cells generated during early placental development?
  2. How does the endometrium regenerate every month in preparation for pregnancy?
  3. How does the endometrium signal to the placenta in health and disease?

With our focus on understanding the stem cell biology of the human endometrium and placenta in health and disease, we aim to generate knowledge that will have implications for reproductive and developmental biology, gynaecology and fetal and maternal health.

Collaborators

Prof. Graham Burton, Dept of PDN, University of Cambridge
Prof. Ashley Moffett, Dept. of Pathology, University of Cambridge
Dr. Myriam Hemberger, Babraham Institute, Cambridge
Prof. John Doorbar, Dept. of Pathology, University of Cambridge
Prof. Hilary Critchley, University of Edinburgh
Prof. Stephen O’Rahilly, Metabolic Research Laboratories, University of Cambridge
Dr. Russell Hamilton, Centre for Trophoblast Research, University of Cambridge
Dr. Sarah Teichmann, Wellcome Trust Sanger Institute, Cambridge
Prof. Ruth Cameron, Dept. of Materials Science & Metallurgy, University of Cambridge
Prof. Serena Best, Dept. of Materials Science & Metallurgy, University of Cambridge
Dr. Budhan Pukazhenthi, Smithsonian Conservation Biology Institute, Virginia

Key Publications

Lee CQE, Turco MY, Gardner L, Simons BD, Hemberger M, Moffett A. 2018. Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta. Development, Apr 16;145(16). pii: dev162305. doi: 10.1242/dev.162305.2.

Turco MY, Gardner L, Hughes J, Cindrova-Davies T, Gomez MJ, Farrell L, Hollinshead M, Marsh SGE, Brosens JJ, Critchley HO, Simons BD, Hemberger M, Koo BK, Moffett A, Burton GJ. 2017 Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology, May;19(5):568-577. doi: 10.1038/ncb3516.

Lee CQ, Gardner L, Turco M, Zhao N, Murray MJ, Coleman N, Rossant J, Hemberger M, Moffett A. 2016. What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast. Stem Cell Reports, Feb 9;6(2):257-72. doi: 10.1016/j.stemcr.2016.01.006.

Simple English

For a successful pregnancy, there must be an efficient dialogue between the uterus (mother) and placenta (baby). Our lab studies this communication to identify and distinguish between the placental and maternal defects that contribute to pregnancy disorders. We use 3D cultures of cells, called organoids, which are very similar in form and function to the placenta and the inner womb (endometrium) tissue. We use organoids to study the fundamental biology of how these two organs grow and function in health and disease.

Above: Immunofluorescent image of human endometrial organoids after hormonal stimulation and stained for secretory cells (glycodelin - red) and ciliated cells (acetylated α-tubulin – yellow). Nuclei counterstained with dapi (blue)


Above: Electron micrograph of ciliated cells in the human endometrial organoids after hormonal stimulation

Above: Immunofluorescent confocal z-stack image of human trophoblast organoid stained for EpCAM (green), EdU (red) and dapi (blue)