Center for Molecular Medicine Cologne

Epigenomic-based identification of major cell identity regulators: an innovative approach


to dissect cellular heterogeneity based on a highly sensitive and specific strategy. The research team of Alvaro Rada-Iglesias, leading a Junior Research Group at the Center for Molecular Medicine Cologne,

Schematic overview using epigenomic-based identification of major cell identity regulators to dissect cellular heterogeneity.

and associated with CECAD Cologne has recently implemented a novel 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 the postdocs Dr. Rizwan Rehimi and Dr. Christina Tebartz and the 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.

A collaborative approach involving colleagues from the CMMC and CECAD
Based on this hypothesis and in collaboration with the colleagues Dr. Mathieu Clément-Ziza (CMMC), PD Dr. Esther Mahabir-Brenner (CMMC) and Dr. 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).

Alvaro Rada-Iglesias comments: "The main application of our method is to uncover the major cell identity regulators of the different cell types that might exist within a heterogeneous cell population. Consequently, our method can be used:

  • to improve our understanding of critical developmental processes, such as patterning
  • to assist in the characterization of adult stem cells, which can improve our understanding of tissues homeostasis and regeneration
  • to dissect tumor heterogeneity by uncovering the major regulators of cancer stem cells residing within tumors.

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 strategy can certainly include tumors, which are typically heterogeneous and contain rare cell populations that have been proposed to drive tumor growth and malignancy.

Dr. Alvaro Rada-Iglesis is leading a Junior Research Group at the CMMC. The Junior Research Group Program is a funding program of the CMMC, which is comparable to the Emmy Noether-Program by the German research Foundation and equivalent to an Assistant Professorship (W1) with a running period of 5 (+3) years.

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),

For further information, please contact:

Dr. Alvaro Rada-Iglesias
Junior Research Group Leader - Developmental Genomics Laboratory
Center for Molecular Medicine Cologne (CMMC), University of Cologne
CECAD-Cluster of Excellence, University of Cologne.
ORCID ID:0000-0001-7137-1341
Robert-Koch Str. 21
50931 Cologne, Germany
tel: +49 (0) 221 478 96 988