In both normal embryonic tissues and tumors, cells physically interact and communicate with each other, which influences their gene expression and thus their function. To uncover how these expression programs are defined, we need to consider the multicellular context in which they occur. Single-cell transcriptomics technologies have revealed an enormous variety of ‘cell states’ in which cells normally considered the same type exhibit marked differences in their transcriptional profile. To uncover which cell states influence each other, we are developing strategies to analyze cells within their tissue context and identify the communication events responsible for specific cellular decisions and behaviors. By expanding the potential of single-cell approaches, our team of experimental and computational scientists is thus aiming to decipher the intimate relationship between cell identity and tissue organization.
A key challenge for the future is to understand how cell-cell interactions influence abnormal tissue growth and organization. Some tumors, for instance, appear to hijack normal developmental programs so that they can progress without the need for additional mutations. In fact, tumor cells from cancers such as neuroblastoma and melanoma are similar to cells normally only found during prenatal development. We aim to better understand how these embryonic gene expression profiles are shaped during normal development and why such similar states are observed in tumor cells. We have a particular interest in the biomedically relevant neural crest lineage of the developing embryo, which can give rise to tumors that exhibit substantial cellular heterogeneity and plasticity. Understanding how cells interact with each other and execute these embryonic programs, will be invaluable for improving the detection of tumor cell heterogeneity and developing more effective treatments.
Grosswendt, S.*, Kretzmer, H.*, Smith, Z.D.*, Kumar A.S., Hetzel, S., Wittler, L., Klages, S., Timmermann, B., Mukherji, S., and Meissner, A.
Epigenetic regulator function through mouse gastrulation
Nature 2020, *equal contribution
Basu, S.*, Mackowiak, S.D.*, Niskanen, H., Knezevic, D., Asimi, V., Grosswendt, S., Geertsema, H., Ali, S., Jerkovic, I., Ewers, H., Mundlos, S., Meissner, A., Ibrahim, D.M., and Hnisz, D.
Unblending of Transcriptional Condensates in Human Repeat Expansion Disease
Cell 2020, *equal contribution
Chan, M.M.*, Smith, Z.D.*, Grosswendt, S., Kretzmer, H., Norman, T.M., Adamson, B., Jost, M., Quinn, J.J., Yang, D., Jones, M.G., Khodaverdian, A., Yosef, N., Meissner, A. and Weissman, J.S.
Molecular recording of mammalian embryogenesis
Nature 2019, *equal contribution