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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.
Zhang YW, Mess J, Aizarani N, Mishra P,  Johnson C,  Romero-Mulero MR, Rettkowski J, Schönberger K, Obier N, Jäcklein K, Woessner NM, Lalioti M, Velasco-Hernandez T, Sikora K, Wäsch R, Lehnertz B,  Sauvageau G, Manke T, Menendez P, Walter SG, Minguet S, Laurenti E, Günther S, Grün D, Cabezas Wallscheid N (2022)
Hyaluronic Acid–GPRC5C Signalling Promotes Dormancy in Hematopoietic Stem Cells
Nature Cell Biology, June 20, 2022
2.
Schönberger K, Obier N, Romero-Mulero MC, Cauchy P,  Mess J, Pavlovich PV, Zhang YW, Mitterer M, Rettkowski J, Lalioti ME, Jäcklein K, Curtis JD, Féret B, Sommerkamp P, Morganti C, Ito K, Ghyselinck NB, Trompouki E, Buescher JM, Pearce EL and Cabezas-Wallscheid N (2022)
Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity
Cell Stem Cell, 29 (1), 131-148.e10.
3.
Sommerkamp P, Romero-Mulero MC, Narr A, Ladel L, Hustin LSP, Schönberger K, Renders S, Altamura S, Zeisberger P, Jäcklein K, Klimmeck D, Rodriguez-Fraticelli AE, Camargo F, Perié L, Trumpp A, Cabezas-Wallscheid N (2021)
Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells
Blood 137 (23), 3218-3224.
4.
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.
5.
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.

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