Joost Gribnau

Joost is full professor and head of the department of Developmental Biology at the Erasmus MC. He also founded the Erasmus MC iPS core facility in 2010, which has so far generated more than 250 patient iPS cell lines providing the basis for a wealth of research at the Erasmus MC. In addition, the Gribnau laboratory has established technology to readout epigenomic, transcriptomic and enhancer changes directing cell fate decisions, that is currently applied to define better culture conditions for directed iPSC differentiation.

Joost has a longstanding interest in understanding regulation of gene expression in relation to cell fate decisions in development and cell differentiation. Initial studies focused on different aspects of the X-chromosome inactivation (XCI) process, that inactivates one X chromosome in every female cell. The Gribnau laboratory unravelled many key steps of the mechanism directing initiation of XCI (Monkhorst et al., Cell 2008, Jonkers et al., Cell 2009, Barakat et al., Mol Cell 2015,Gontan et al., Nature 2012 and Nature comm. 2018). Recent work focusses on the identification of new XCI regulatory factors (van Bemmel et al. Nat Genet. 2019). To study epigenetic changes in development, the Gribnau laboratory developed several new technologies including MeD-seq and DCM-TM to determine genome wide DNA methylation profiles (MeDseq) and retrieve gene and enhancer activity maps of past expression (DCM-TM) (Boers Genome Res. 2018, submitted). These form the basis for more than 50 collaborations worldwide. The technology has been licensed to Methylomics B.V., that applies the MeD-seq for marker discovery studies in cancer. The Gribnau laboratory has published many papers on human disease modelling using iPSCs, and knowledge obtained is translated and implemented into the iPS facility. At present the group focuses on understanding cell signalling directing cell fate decisions to be translated to improved iPSC differentiation protocols.

Relevant publications

• van Bemmel JG, Gard C, Galupa R, Servant N, Picard C, Davies J, Szempruch T, Zhan Y, Baulande S, Gentien S, Nora EP, Giorgetti L, Guttman M, Hughes J, Higgs D, Gribnau J, Heard E (2019). The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist. Nat Genet 51:1024-1034
• Boers R, Boers J, de Hoon B, Kockx C, Ozgur Z, Molijn A, van IJcken W, Laven J, Gribnau J (2018). Genome-wide DNA methylation profiling using the methylation-dependent restriction enzyme LpnPI. Genome Res 28:88-99
• Barakat TS, Ghazvini M, de Hoon B, Li T, Eussen B, Douben H, van der Linden R, van der Stap N, Boter M, Laven JS, Galjaard RJ, Grootegoed JA, de Klein A, Gribnau J (2015). Stable X chromosome reactivation in female human-induced pluripotent stem cells. Stem Cell Rep 4:199-208
• Gontan C, Achame EM, Demmers J, Barakat TS, Rentmeester E, van IJcken W, Grootegoed JA, Gribnau J (2012). RNF12 initiates X chromosome inactivation by targeting REX1 for degradation. Nature, 485:386- 390.
• Jonkers I, Barakat TS, Achame EM, Monkhorst K, Kenter A, Rentmeester E, Grosveld F, Grootegoed JA, Gribnau J (2009). RNF12 is a X-encoded dose-dependent activator of X inactivation. Cell, 139:999-1011.