Head of the group: Susana Chuva de Sousa Lopes PhD
Research technician: L.van Iperen
PhD students: M. Fernandes (FCT, Portugal), M. Roost (Bontius Stichting, Netherlands),
A. Melo Bernardo (FCT, Portugal), N. He (CSC, China),
Postdocs: M. Bialecka, F. Wang
Main research themes:
- Human and mammalian early development and organogenesis
- Gain and loss of pluripotency
- Germline development and gamete maturation
- Epigenetic mechanisms during development
- Transcriptional analysis of differentiation using mathematical algorithms
We are interested in understanding how differentiation and lineage commitment occurs in vivo and in vitro in different species, but in particular in humans. In the past few years, we have generated transcriptional profiles via next-generation sequencing (NGS) of over a hundred different human (fetal) organs, including first and second trimester organs. Based on this data, we have developed a mathematical algorithm called KeyGenes (Roost et al., 2015) to facilitate the comparison of transcriptional data from differentiated human pluripotent stem cells (hPSCs) and their in vivo counterparts during development and adulthood. Our datasets and analysis code is freely available on an open-access website (http://www.keygenes.nl/). This open-source tool allows users to benchmark their cells/organoids against their organs of interest and predicts both tissue identity and maturation level of the input samples. In particular, KeyGenes proved essential to demonstrate the fidelity of kidney organoids derived from hPSCs (Takasato et al., 2015).
We specialised in the microdissection of early embryos (both human and mouse), with a particular focus on the development of human germ cells, as these cells undergo extensive epigenetic remodeling and are an excellent system to understand gain and loss of pluripotency.
We have the ethics approval in the Netherlands and the infrastructure to collect and store the material and have been dissecting and archiving this material for several years. This has resulted in several publications on transcriptomics (Roost et al., 2015) and also DNA methylomics (Slieker et al., 2015).
Slieker, Roost, van Iperen, Suchiman, Tobi, Carlotti, de Koning, Slagboom, Heijmans*, Chuva de Sousa Lopes*. DNA methylation landscapes of human foetal development (2015). PLoS Genet, e1005583.
Van der Jeught, O’Leary, Duggal, de Sutter, Chuva de Sousa Lopes*, Heindryckx*. The post-inner cell mass intermediate: implications for stem cell biology and assisted reproductive technology (2015). Hum Reprod Update 21:616-626.
Takasato, Er, Chiu, Maier, Baillie, Ferguson, Parton, Wolvetang, Roost, Chuva de Sousa Lopes, Little. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis (2015). Nature, 526:564-568; comment in Nature, 526:512-3.
Roost, van Iperen, Ariyurek, Buermans, Arindrarto, Devalla, Passier, Mummery, Carlotti, de Koning, van Zwet, Goeman, Chuva de Sousa Lopes (2015). KeyGenes, a tool to probe tissue differentiation using a human fetal transcriptional atlas. Stem Cell Rep 4:1112-24.
Duggal, Warrier, Ghimire, Broekaert, Van der Jeught, Lierman, Deroo, Peelman, Van Soom, Cornelissen, Menten, Mestdagh, Vandesompele, Roost, Slieker, Heijmans, Deforce, De Sutter, De Sousa Lopes*, Heindryckx* (2015). Alternative routes to induce naïve pluripotency in human embryonic stem cells. Stem Cells 33:2686-98.
O'Leary, Heindryckx, Lierman, van Bruggen, Goeman, Vandewoestyne, Deforce, Chuva de Sousa Lopes*, de Sutter*. Tracking the progression of the human inner cell mass during embryonic stem cell derivation (2012). Nat Biotechnol, 30, 278-782; comment in Nat Biotechnol, 30:247-9.
Hayashi*, Chuva de Sousa Lopes*, Tang, Surani. Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states (2008). Cell Stem Cell, 3, 391-401.
Cree, Samuels, Chuva de Sousa Lopes, Rajasimha, Wonnapinij, Mann, Dahl, Chinnery. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes (2008). Nat Genet, 40, 249-254; comment in Nat Genet, 40:134-5.
Brons, Smithers, Trotter, Rugg-Gunn, Sun, Chuva de Sousa Lopes, Howlett, Clarkson, Ahrlund-Richter, Pederson, Vallier. Derivation of pluripotent epiblast stem cells from mammalian embryos (2007). Nature, 448, 191-5.
Hayashi, Chuva de Sousa Lopes, Surani. Germ cell specification in mice (2007). Science, 316, 394-6.