Laboratory Nina Cabezas-Wallscheid

Laboratory Nina Cabezas-Wallscheid

Regulation of Hematopoietic Stem Cell Dormancy

We investigate the mechanism by which some dietary components regulate the epigenetic and metabolic state of hematopoietic stem cell dormancy.

Adult hematopoietic stem cells (HSCs) have the unique potential to generate multipotent progenitors, which can differentiate into mature blood cells. A sub-population within the HSC pool comprises of deeply quiescent cells referred to as dormant HSCs. Dormant stem cells harbor the highest long-term reconstitution potential within the hematopoietic system upon transplantation experiments and serve as a reserve pool used in emergency situations. For instance, upon viral infections or severe loss of blood, dormant HSCs exit their quiescent state to produce downstream progenitors. Still constant activation of dormant HSCs can lead to hematological malignancies. Thus, it is fundamental to study how stem cell dormancy is regulated and maintained. During the last few years it has become evident that metabolites are not only a consequence of transcriptional programs but rather play an active role in regulating cell fate. In particular it was proven that vitamins are essential co-factors of enzymes thus regulating the epigenome.

Goal

Our final goal is to provide unique in-depth insight into the functional signaling networks that regulate HSC fate while pioneering therapeutic avenues for nutritional and hematological diseases

Approach

To address these biological questions, we have established state-of-the-art OMICs (transcriptome, metabolome, chromatin accessibility and immunoprecipitation) and single-cell techniques which are opening up unprecedented avenues to study the metabolic and epigenetic features of rare cell populations such as dormant HSCs. We are pursuing interdisciplinary projects which include the use of genetic mouse models, primary patient material in combination with comprehensive bioinformatic analysis.


Selected Publications

1.
Sommerkamp P, Altamura S, Renders S, Narr A, Ladel L, Zeisberger P, Eiben PL, Fawaz M, Rieger MA, Cabezas-Wallscheid N*, Trumpp A* (2020)
Differential alternative polyadenylation landscapes mediate hematopoietic stem cell activation and regulate glutamine metabolism
Cell Stem Cell 26(5), 722-738.e7

*co-last author & co-corresponding author
2.
Cabezas-Wallscheid N, Buettner F, Sommerkamp P, Klimmeck P, Ladel L, Thalheimer FB, Pastor-Flores D, Roma LP, Renders S, Zeisberger P,  Przybylla A, Schönberger K, Scognamiglio R, Altamura S, Florian KM, Fawaz M, Vonficht D, Tesio M, Collier P, Pavlinic D, Geiger H, Schroeder T, Benes V, Dick TP, Rieger MA, Stegle O, Trumpp A (2017)
Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy
Cell 169(5), 807-823.
3.
Scognamiglio R, Cabezas-Wallscheid N, Thier MC, Altamura S, Reyes A, Prendergast ÁM, Baumgärtner D, Carnevalli LS, Atzberger A, Haas S, von Paleske L, Boroviak T, Wörsdörfer P, Essers MA, Kloz U, Eisenman RN, Edenhofer F, Bertone P, Huber W, van der Hoeven F, Smith A, Trumpp A. (2016)
Myc depletion induces a pluripotent dormant State mimicking diapause
Cell 164(4), 668-680.
4.
Cabezas-Wallscheid N*, Klimmeck D*, Hansson J*, Lipka DB*, Reyes A*, Wang Q, Weichenhan D, Lier A, von Paleske L, Renders S, Wünsche P, Zeisberger P, Brocks D, Gu L, Herrmann C, Haas S, Essers MA, Brors B, Eils R, Huber W, Milsom MD, Plass C, Krijgsveld J, Trumpp A. (2014)
Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis
Cell Stem Cell 15(4), 507-522.

* equal contribution
5.
Cabezas-Wallscheid N, Eichwald V, de Graaf J, Löwer M, Lehr HA, Kreft A, Eshkind L, Hildebrandt A, Abassi Y, Heck R, Dehof AK, Ohngemach S, Sprengel R, Wörtge S, Schmitt S, Lotz J, Meyer C, Kindler T, Zhang DE, Kaina B, Castle JC, Trumpp A, Sahin U, Bockamp E. (2013)
Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model
EMBO Molecular Medicine 5(12), 1804-1820.

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