LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells.

Höpner, S. S.; Raykova, Ana; Radpour, R.; Amrein, M. A.; Koller, D.; Bärlocher, G. M.; Riether, C.; Ochsenbein, A. F. (2021). LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells. Nature Communications, 12(1), p. 1065. Springer Nature 10.1038/s41467-021-21317-x

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The production of blood cells during steady-state and increased demand depends on the regulation of hematopoietic stem cell (HSC) self-renewal and differentiation. Similarly, the balance between self-renewal and differentiation of leukemia stem cells (LSCs) is crucial in the pathogenesis of leukemia. Here, we document that the TNF receptor superfamily member lymphotoxin-β receptor (LTβR) and its ligand LIGHT regulate quiescence and self-renewal of murine and human HSCs and LSCs. Cell-autonomous LIGHT/LTβR signaling on HSCs reduces cell cycling, promotes symmetric cell division and prevents primitive HSCs from exhaustion in serial re-transplantation experiments and genotoxic stress. LTβR deficiency reduces the numbers of LSCs and prolongs survival in a murine chronic myeloid leukemia (CML) model. Similarly, LIGHT/LTβR signaling in human G-CSF mobilized HSCs and human LSCs results in increased colony forming capacity in vitro. Thus, our results define LIGHT/LTβR signaling as an important pathway in the regulation of the self-renewal of HSCs and LSCs.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Höpner, Sabine; Raykova, Ana Plamenova; Radpour, Ramin; Bärlocher, Gabriela Maria and Riether, Carsten

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

13 Oct 2021 08:29

Last Modified:

10 Jun 2022 07:33

Publisher DOI:

10.1038/s41467-021-21317-x

PubMed ID:

33594067

BORIS DOI:

10.48350/159617

URI:

https://boris.unibe.ch/id/eprint/159617

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