Disturbed trophoblast transition links early fetal to maternal syndrome progression in pre-eclampsia
Authors/Creators
- Nonn, Olivia1
- Debnath, Olivia2
- Valdes, Daniela S.3
- Sallinger, Katja4
- Secener, Kerim5
- Haider, Sandra6
- Fischer, Cornelius7
- Tiesmeyer, Sebastian2
- Nimo, Jose8
- Kuenzer, Thomas9
- Maxian, Theresa10
- Knöfler, Martin10
- Karau, Philipp2
- Bartolomaeus, Hendrik11
- Kroneis, Thomas4
- Frolova, Alina12
- Neuper, Lena13
- Haase, Nadine14
- Kräker, Kristin15
- Kedziora, Sarah15
- Forstner, Désirée16
- Verlohren, Stefan17
- Stern, Christina18
- Cosica, Fabian8
- Sugulle, Meryam19
- Jones, Stuart20
- Tilaganathan, Basky21
- Eils, Roland2
- Huppertz, Berthold16
- El-Heliebi, Amin4
- Staff, Anne Cathrine19
- Müller, Dominik N.15
- Dechend, Ralf22
- Gauster, Martin16
- Ishaque, Naveed2
- Herse, Florian3
- 1. Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria; Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin, Berlin, Germany; Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- 2. Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Digital Health Center, Berlin, Germany
- 3. Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin, Berlin, Germany; Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- 4. Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria; Centre for Biomarker Research in Medicine (CBmed), Graz, Austria
- 5. Institute for Medical Systems Biology (BIMSB), Berlin, Germany; Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Germany
- 6. Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria
- 7. Institute for Medical Systems Biology (BIMSB), Berlin, Germany
- 8. Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- 9. Institute of Statistics, University of Technology Graz, Austria
- 10. Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Austria
- 11. Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Germany
- 12. Institute of Molecular Biology and Genetic of NASU, Kyiv, Ukraine
- 13. Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Austria
- 14. Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin, Berlin, Germany; Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany
- 15. Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin, Berlin, Germany; Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany
- 16. Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria;
- 17. Department of Obstetrics and Gynaecology, Charité – Universitätsmedizin Berlin, Germany
- 18. Department of Obstetrics and Gynaecology, University Hospital Graz, Medical University Graz, Austria
- 19. Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway
- 20. Clinical Biochemistry, King George's Hospital, London, UK
- 21. Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, London, UK
- 22. Experimental and Clinical Research Center, a cooperation between the Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association and the Charité ‐ Universitätsmedizin Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin, Berlin, Germany; Max‐Delbrück‐Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany; HELIOS Clinic, Department of Cardiology and Nephrology, Berlin, Germany
Description
Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality, and life-long complications (1). We currently lack efficient screening tools (2,3) and early therapies (4,5) to address PE. To study the initial stages of early onset PE, and identify candidate markers and pathways, we performed spatio-temporal multi-omics profiling of human PE placentae and healthy controls and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-seq approach combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses.
This repository contains microscopy and ISS data used in the study. It contains the 113 TIFF files and 2 vsi files produced on a digital slide scanner (Olympus SLIDEVIEW VS200) connected to external LED source (Excelitas Technologies, X-Cite Xylis) and the MATLAB output files.
References
1 Williams, D. Long-term complications of preeclampsia. Semin Nephrol 31, 111-122,
doi:10.1016/j.semnephrol.2010.10.010 (2011).
2 Brown, M. A. et al. Hypertensive Disorders of Pregnancy: ISSHP Classification,
Diagnosis, and Management Recommendations for International Practice.
Hypertension 72, 24-43, doi:10.1161/HYPERTENSIONAHA.117.10803 (2018).
3 Zeisler, H. et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected
Preeclampsia. N Engl J Med 374, 13-22, doi:10.1056/NEJMoa1414838 (2016).
4 Hauth, J. C. et al. Pregnancy outcomes in healthy nulliparas who developed
hypertension. Calcium for Preeclampsia Prevention Study Group. Obstet Gynecol 95,
24-28, doi:10.1016/s0029-7844(99)00462-7 (2000).
5 Phipps, E. A., Thadhani, R., Benzing, T. & Karumanchi, S. A. Pre-eclampsia:
pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 15, 275-289,
doi:10.1038/s41581-019-0119-6 (2019).
Funding Details:
F. H. and D.N.M. were supported by Deutsche Forschungsgemeinschaft (HE6249/5-1; HE6249/7-1; HE6249/7-2; D.N.M.: Projektnummer 394046635 - SFB 1365). D.N.M. was supported by grants from the German Centre for Cardiovascular Research (DZHK; BER 1.1 VD). O. N. was supported through the PhD program Inflammatory Disorders in Pregnancy (DP-IDP) by the Austrian Science Fund (FWF): Doc 31-B26, PhD program Molecular Medicine at the Medical University of Graz, and through the Marietta Blau Grant by the Austrian Federal Ministry for Education, Science and Research (OeAD; BMBWF), and with grants from the MeFo Graz (PS-Stipendium 2019/2020), German Association of Prenatal Diagnostics and Obstetrics (DGPGM, 2020). K.S., T.K. and A.E-H. were supported by the K1 COMET Competence Center CBmed (Center for Biomarker Research in Medicine), which is funded by the Federal Ministry of Transport, Innovation and Technology (BMVIT), Land Steiermark (Department 12, Business and Innovation), BMWFW, the Styrian Business Promotion Agency (SFG), and the Vienna Business Agency. The COMET programme is executed by the Austrian Research Promotion Agency (FFG).
K.S. was supported by the Doctoral School in Translational Molecular and Cellular Biosciences at the Medical University of Graz.
M.G. was supported by the FWF: (P 29639, P33554, I 3304, and Doc 31-B26) and the Medical University Graz through the PhD programs Inflammatory Disorders in Pregnancy (DP-IDP) and MolMed. B.H. was supported by the FWF: (Doc 31-B26) and the Medical University Graz through the PhD program Inflammatory Disorders in Pregnancy (DP-IDP). Sebastian Tiesmeyer was supported by Federal Ministry of Education and Research of Germany in the framework of SAGE (031L0265). This work was supported by the BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI)
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Additional details
Funding
- FWF Austrian Science Fund
- The role of angiotensin II on placental fractalkine I 3304