Research profile

Astrocytes are the most abundant glial cell type in the brain.  For decades they were considered as merely supportive cells in the central nervous system. However, the discovery of the critical role of these cells in the generation and pruning of synapses challenged this view. Astrocytes are currently viewed as essential regulators of brain plasticity. Morphological and functional analyses revealed remarkable differences between human and mouse astrocytes, suggesting a possible role in brain evolution. Our primary aim is to decipher the regulatory circuit orchestrating astrocyte biology and to identify the genetic changes that underlie astrocyte functional diversification throughout mammalian evolution. We use both in-vivo and stem cell models. We apply multiple -omics approaches (RNA-seq, ChIP-seq, ATAC-seq, in-situ Hi-C) to measure the activity of genes and to identify regulatory elements controlling their expression. We take advantage of CRISPR-Cas9 systems to disturb genes and regulatory elements and to measure the impact of these genetic modifications on brain biology. As an integral part of our research, we use and develop computational tools to uncover the transcriptional regulatory network controlling cell fate and to gauge the functional impact of the three-dimensional organization of regulatory elements in the cell nucleus on the control of gene expression. More information can be found on the laboratory’s webpage:  https://pekowskalab.nencki.edu.pl/

Current research activities

• Identification of the regulatory network orchestrating gene expression patterns in astrocytes
• Isolation of genetic drivers of evolutionary changes in the biology of astrocytes
• Establishment of the role of the three-dimensional structure of chromatin in gene regulation
• Development of computational tools for analysis of chromatin topology

Selected publications

Pękowska A., Klaus B, Xiang W., Severino J., Daigle N., Klein F.A., Oleś M., Casellas R., Ellenberg J., Steinmetz L.M.S., Bertone P. * and Huber W.* Gain of CTCF-anchored chromatin loops marks the exit from naive pluripotency. Cell Systems Nov. 28; 7(5):482-495

Vian L.#, Pękowska A.#, Rao SSR.#, Kieffer-Kwon K-R#, Jung S#, Baranello L., Huang SC., El Khattabi L., Dose M., Pruett N., Sanborn AL., Canela A., Maman Y., Oksanen A., Resch W., Li X., Lee B., Kovalchuk AL., Tang Z., Nelson S., Di Pierro M., Cheng RR., Machol I., St Hilaire BG., Durand NC., Shamim MS., Stamenova EK., Onuchic JN., Ruan Y., Nussenzweig A., Levens D., Aiden EL., Casellas R. The energetics and physiological impact of cohesin extrusion. Cell 2018 May 17;173(5):1165-1178.e20.

Schwarzer W.#, Abdennur N.#, Goloborodko A.#, Pękowska A., Fudenberg G., Loe-Mie Y., Fonseca N.A., Huber W, Haering C., Mirny L., Spitz F. Two independent modes of chromosome organization are revealed by cohesin removal. Nature 2017 Nov 2;551(7678):51-56

Pękowska A.#, Benoukraf T.#, Zacarias-Cabeza J.#, Belhocine M., Koch F., Holota H., Imbert J. Andrau JC., Ferrier P., Spicuglia S. H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 2011;(July):1–13.

Pękowska A., Benoukraf T., Ferrier P., Spicuglia S. A unique H3K4me2 profile marks tissue-specific gene regulation. Genome Research, 2010 Nov; 20(11):1493–502.

# equal contribution
* corresponding author