New publication by Alvaro Rada-Iglesias: Epigenomic-based identification of major cell identity regulators
The research group of Dr. Alvaro Rada-Iglesias (Center for Molecular Medicine Cologne (CMMC) and CECAD, University of Cologne, Germany) has recently implemented a novel, simple and universal approach that enables the functional and global dissection of cellular heterogeneity in a broad range of biological and pathological contexts. Their findings were recently published in the journal Cell Reports.
Embryonic and adult tissues display high cellular heterogeneity, as they typically contain multiple and functionally distinct cell types. This cellular heterogeneity is required for tissue formation and function, which are altered in multiple birth defects and age-related diseases, respectively. Therefore, the molecular and functional dissection of cellular heterogeneity has major biological and medical implications. However, investigating and understanding all the different cells that conform a tissue is like finding a needle in a haystack: each tissue has many cell types and some of those cell types occur in very low abundance.
To overcome these problems, Dr.Alvaro Rada-Iglesias and his team, including postdocs Dr.Rizwan Rehimi and Dr.Christina Tebartz and PhD students Milos Nikolic and Sara de la Cruz Molina, hypothesized that genes expressed in a heterogeneous manner within a given tissue could be readily identified based on the simultaneous presence of both activating and repressive features. Based on this hypothesis and in collaboration with Mathieu Clément-Ziza(CMMC), Esther Mahabir (CMMC) and Peter Frommolt (CECAD), the Rada-Iglesias laboratory implemented a simple, yet highly sensitive and specific strategy whereby the major cell identity regulators of the different cell populations found within any tissue of interest can be globally and seemingly predicted.
To illustrate the performance and broad applicability of this novel approach, the Rada-Iglesias team investigated the heterogeneity found within different embryonic tissues (spinal neural tube, brain, limbs) and model organisms (chicken and mouse embryos). In the near future it should be possible to apply this strategy to other biological and pathological contexts in which cellular heterogeneity is known to be of functional relevance. This can certainly include tumors, which are typically heterogeneous and contain rare cell populations that have been proposed to drive tumor growth and malignancy.
Original Publication:
Rehimi R, Nikolic M, Cruz-Molina S, Tebartz C, Frommolt P, Mahabir E, Clément-Ziza M and Rada-Iglesias A. Epigenomic-based identification of major cell identity regulators within heterogeneous embryonic cell populations. Cell Reports (2016), http://dx.doi.org/10.1016/j.celrep.2016.11.046
Image caption:
Levels of MNR2, a bona fide marker of differentiated motorneurons, were investigated by immunofluorescence in the spinal neural tube of chicken embryos. Chicken embryos were unilaterally electroporated with vectors expressing GFP (GFP ctrl) or ZNF488 and GFP (ZNF488 OE). The electroporated side is shown to the right.