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

S. S. Höpner, Ana Raykova, R. Radpour, M. A. Amrein, D. Koller, G. M. Baerlocher, C. Riether and A. F. Ochsenbein ()
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S. S. Höpner: University of Bern
Ana Raykova: University of Bern
R. Radpour: University of Bern
M. A. Amrein: University of Bern
D. Koller: University of Bern
G. M. Baerlocher: University of Bern
C. Riether: University of Bern
A. F. Ochsenbein: University of Bern

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21317-x

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DOI: 10.1038/s41467-021-21317-x

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