My group investigates the developmental trajectories of human organs and tissues, with a particular interest for the urogenital system and gametogenesis. This has resulted in several publications on transcriptomics (Roost et al., 2015, 2017), DNA methylomics (Slieker et al., 2015) and histological analysis (Heeren et al., 2016).
Aim and focus
Based on the transcriptional profiles of over a hundred different human (fetal) organs, including the kidney, 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 and their in vivo counterparts. Our datasets and analysis code are freely available on an open-access website (www.keygenes.nl). Keygenes proved of value to demonstrate the fidelity of kidney organoids derived from human induced pluripotent stem cells (iPSCs) and resulted in a successful collaborative effort between my group and the group of Prof. Melissa Little (Takasato et al., 2015).
We are now performing a detailed study of the cellular networks and molecular pathways that control development and maturation of the oocyte within the human ovary, combining genomics with single-cell transcriptomics to study epigenetic reprogramming with in vitro culture.
Collaboration within the LUMC
Prof. J. Goeman, MSTAT – biostatistics/Keygenes
Prof. C. Mummery, ANA – iPSC facility
Prof. F. Koning, IHB - CyTOF
Dr. M. Goncalves, MCB – CRISPR-CAS technology, chromosomal instability
Dr. L. vd Westerlakken, GYN – cryopreservation human ovaries
SASC/LGTC – sequencing and primary analysis
Collaboration with Prof. A. van Oudenaarden (Hubrecht Institute) on single-cell transcriptomics (see Nat Commun, in press here bellow) and with Prof. H. Clevers (Hubrecht Institute) on organoid culture of several organs.
I am supervising a PhD together with Prof. S. Repping and Dr. G. Hamer (AMC), on germ cell differentiation.
I am Visiting Professor in the Dept. Reproductive Medicine, Ghent University Hospital, Ghent, Belgium (0.05 fte, 2013-present)
Grants and other funding
MSCA-COFUND ResCUE (MSCA-COFUND-2018-801540). Co-PI
KWF (KWF-2018-11307). Co-PI
ERC (ERC-CoG-2016-725722). PI
Vértesy A, Arindrarto W, Roost MS, Reinius B, Torrens-Juaneda V, Bialecka M, Moustakas I, Ariyurek Y, Kuijk E, Mei H, Sandberg R, van Oudenaarden A* and Chuva de Sousa Lopes SM* (2018). Parental haplotype specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells. Nature Communication, in press
Roost MS, Slieker RC, Bialecka M, van Iperen L, Gomes Fernandes MM, He N, Suchiman HED, Szuhai K, Carlotti F, de Koning EJP, Mummery CL, Heijmans BT, Chuva de Sousa Lopes SM (2017). DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells. Nat Commun 8:908 Geens M, Chuva De Sousa Lopes SM (2017). X chromosome inactivation in human pluripotent stem cells as a model for human development: back to the drawing board? Human Reproduction Update 23:520-532 Slieker RC, Roost MS, van Iperen L, Suchiman HE, Tobi EW, Carlotti F, de Koning EJ, Slagboom PE, Heijmans BT*, Chuva de Sousa Lopes SM* (2015). DNA Methylation Landscapes of Human Fetal Development. Plos Genet e1005583 Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH (2015). Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526:564-568Roost MS, van Iperen L, Ariyurek Y, Buermans HP, Arindrarto W, Devalla HD, Passier R, Mummery CL, Carlotti F, de Koning EJ, van Zwet EW, Goeman JJ, Chuva de Sousa Lopes SM (2015). KeyGenes, a tool to probe tissue differentiation using a human fetal transcriptional atlas. Stem Cell Reports 4:1112-24