Cell Fate Decisions of Epithelial Development and Disease Group

The group of Jo Zhou (part of RIMLS-Science) investigates stem cell fate, proliferation, and differentiation to understand human development and disease.

Research focus

We currently focus on investigating cell fate control mechanisms of human epithelial stem cells, their derived in vitro model models and their translational potential including drug discovery and tissue regeneration. We apply (single-cell) multi-omics and computational integrative analyses on human pluripotent stem cells and adult stem cells, to identify key transcription factors that drive cell fates and their regulatory mechanisms in the epigenetic and the chromatin landscape. 

These studies provide molecular insights into cell differentiation, normal development and disease mechanisms. With these insights, we manipulate the cell fates for cell therapy and tissue regeneration, and identify therapeutic strategies.

Epidermal cell fate in skin development and disease

  • Molecular mechanisms driving epidermal keratinocyte commitment and terminal differentiation.
  • Molecular mechanisms of skin diseases
  • Optimisation of in vitro skin models.

Corneal development and disease

  • Molecular mechanisms driving corneal cell fates
  • Molecular mechanisms of corneal diseases
  • Therapeutic discoveries for corneal diseases including compounds and cell therapy

Projects

  • ZonMw Open (09120012010039) (2021-2026). CorneaRegID: Cornea regeneration instructed by molecular cell identity characterization.
  • Velux Stiftung Ophthalmology project (2021-2023). Autologous cornea regeneration through non-integrative transdifferentiation.
  • European Joint Program Rare Disease (EJP RD) Joint transnational Call (JTC2020) (2021-2024)
  • Health Holland PPP program Human measurement models (2020-2024)
  • International consortium: COST Action: ANIRIDIA-NET, CA18116

Publications

  • Identification of the regulatory circuit governing corneal epithelial fate determination and disease. Smits JGA, Cunha DL, Amini M, Bertolin M, Laberthonnière C, Qu J, Owen N, Latta L, Seitz B, Roux LN, Stachon T, Ferrari S, Moosajee M, Aberdam D, Szentmary N, van Heeringen SJ, Zhou H. PLoS Biol. 2023 Oct 19;21(10):e3002336.  Full text
  • Single-Cell RNA Sequencing: Opportunities and Challenges for Studies on Corneal Biology in Health and Disease. Arts JA, Laberthonnière C, Lima Cunha D, Zhou H. Cells 2023, 12(13), 1808;  Full text
  • scANANSE gene regulatory network and motif analysis of single-cell clusters. Smits JGA, Arts JA, Frölich S, Snabel RR, Heuts BMH, Martens JHA, van Heeringen SJ, Zhou H. F1000Research 2023, 12:243 Full text
  • ANANSE: An enhancer network-based computational approach for predicting key transcription factors in cell fate determination. Xu Q, Georgiou G, Frölich S, van der Sande M, Veenstra GJC, Zhou  H#, van Heeringen SJ#. Nucleic Acids Research. 2021; 49(14):7966-7985.   Full text
  • Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome. Soares E, Xu Q, Li Q, Qu J, Zheng Y, Raeven HHM, Brandao KO, Petit I, van den Akker WMR, van Heeringen SJ, Aberdam D, Tang F, Zhou H. Proc Natl Acad Sci U S A. 2019 116 (35):17361-17370.  Full text

Members

Principal Investigator: Jo Zhou

Postdocs: Dulce Lima Cunha

PhD students: Julian Arts, Luca Meesters, Felicitas Pardow

Technician: Yavuz Kilic

See also