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Regulation of hematopoietic stem cell dormancy

Presentation

Organizer: IRB BioMed Seminars

Date: Thursday 27 October, 5pm
Place: Felix Serratosa Hall, PCB

Speaker: Nina Cabezas-Wallscheid, Ph.D. Group Leader, Regulation of Hematopoietic Stem Cell Dormancy, Max Planck Institute, Freiburg, Germany.

Title: "Regulation of hematopoietic stem cell dormancy"

 

Abstract:

Bone marrow hematopoietic stem cells (HSCs) are vital for the maintenance of hematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the hematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Still, whether HSC dormancy exists in human remains unclear. Our recent work shows the existence and relevance of dormancy in human HSCs and identifies the hyaluronic acid-GPRC5C signalling axis as an essential component controlling the HSC state (Zhang et al., Nature Cell Biology 2022). Further, HSCs rely on complex 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 established and integrated low-input multi-layer OMICs data revealing distinct metabolic and epigenetic hubs that are enriched in HSCs and their downstream multipotent progenitors (Schönberger et al., Cell Stem Cell 2022). 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.

References

Yu Wei Zhang, Julian Mess, Nadim Aizarani, Pankaj Mishra, Carys Johnson, Mari Carmen Romero-Mulero, Jasmin Rettkowski, Katharina Schönberger, Nadine Obier, Karin Jäcklein, Nadine M. Woessner, Talia Velasco-Hernandez, Katarzyna Sikora, Ralph Wäsch, Bernhard Lehnertz, Guy Sauvageau, Thomas Manke, Pablo Menendez, Sebastian Gottfried Walter, Susana Minguet, Elisa Laurenti, Stefan Günther, Dominic Grün, Nina Cabezas Wallscheid.

Hyaluronic acid –GPRC5C signalling promotes dormancy in hematopoietic stem cells. Accepted for publication in Nature Cell Biology

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. 10.1016/j.stem.2021.10.002.

 

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