Marking cancer stem cells in human cancer organoids

Phenotypic heterogeneity in tumors includes non-genetic processes, such as different cell fates and phenotypes due to variable expression patterns. These are either established by tumor intrinsic cues, e.g. cellular differentiation hierarchy, or upon interaction with the tumor microenvironment.

The exact interplay between genetic and non-genetic factors remains elusive with respect to tumor growth, progression and therapy resistance.

The role and consequence of having multiple cell types within a cancer is mostly centered towards the function of cancer stem cells (CSCs) since they are the driving forces of tumor growth. However, the exact signaling cues that support CSC function remain to be understood. For instance, what are the roles of differentiated tumor cells in relation to CSC support? We study cell-cell communication between different cell types in human colorectal cancers (CRCs). Our lab developed markers to label CSCs in patient-derived CRC organoids (PDOs) for high-resolution live imaging of their cellular behavior and cell fate dynamics. Currently, we aim to obtain insights in signaling pathway activities that support tumor growth in real-time, at the quantitative level and with cellular resolution in 3-dimensional organoids.

  • Schepers, Snippert et al., Science 2011
  • Snippert, Schepers et al., EMBO rep 2014
  • Oost et al., Cell rep 2018
Testing cancer stem cells (green) in vivo by lineage tracing (blue ribbon)