#IDIBELLseminars: Regulation of hematopoietic stem cell dormancy

Hematopoietic Stem Cells (HSCs) rely on complex metabolic and epigenetic regulatory networks to preserve their function. Due to the scarcity of HSCs, technical challenges have limited our insights into the interplay between HSC metabolism and their transcriptional and epigenetic regulation. We recently have established new low-input multi-layer OMICs methods to address the metabolic, lipid and epigenetic profiles of mouse and human HSCs and their downstream progenitors, upon aging and leukemia (Schönberger*, Obier* et al., Cell Stem Cell 2022; Lalioti*, Romero-Mulero* et al., revisions). Mechanistically, we uncover a non-classical retinoic acid signaling axis that regulates HSC identity. Our findings emphasize how a single metabolite controls stem cell fate by instructing epigenetic and transcriptional attributes. Now, we have used these knowledge to in vivo modulate HSC activity upon myocardial infraction, thus emergency hematopoiesis, to improve the heart function (Rettkowski*, Romero-Mulero* et al., Nature Cell Biology 2025, accepted). Further, we have recently shown that GPRC5C is a regulator of human HSC dormancy (Zhang et al., Nature Cell Biology 2022). High GPRC5C levels in AML correlate with poor survival and promote leukemia aggression via NF-κB activation and increased branched-chain amino acids (BCAAs; Zhang et al., Blood Advances 2023). Our findings suggest the GPRC5C-NF-κB-SLC7A5-BCAA axis as a therapeutic target in leukemia.

Hosted by Elisa Espinet Hernández – Pancreatic cancer group

Prof. Dr. Nina Cabezas-Wallscheid started her group at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany in 2017. She was appointed in 2023 as full professor at the ETH Zürich, Switzerland. Her group studies how hematopoietic stem cell dormancy is regulated in healthy and in the context of hematological, nutritional disorders and aging. They pursue interdisciplinary projects that include the use of genetic models, dietary treatments and primary human patient material in combination with the development of state-of-the-art omics, single-cell techniques and bioinformatic analysis. Dr. Cabezas-Wallscheid received an ERC Consolidator (2023), ERC Starting Grant (2017), and is part of the EMBO Young Investigator Program since 2022. She was honored with the Janet Rowley Award by the International Society of Experimental Hematology (2023) and the German Stem Cell Network Young Investigator Award (2018). She conducted her postdoctoral work in the laboratory of Prof. Trumpp at the German Cancer Research Center in Heidelberg, Germany. She gained her PhD at the Medical Center of Mainz under the supervision of Dr. Bockamp and studied biotechnology at the Autonomous University of Barcelona, Spain.