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@ARTICLE{Zioni:275374,
author = {N. Zioni and A. A. Bercovich and N. Chapal-Ilani and T.
Bacharach and N. Rappoport and A. Solomon and R. Avraham and
E. Kopitman and Z. Porat and M. Sacma and G. Hartmut and M.
Scheller and C. Müller-Tidow$^*$ and D. Lipka$^*$ and E.
Shlush and M. Minden and N. Kaushansky and L. I. Shlush},
title = {{I}nflammatory signals from fatty bone marrow support
{DNMT}3{A} driven clonal hematopoiesis.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00740},
pages = {2070},
year = {2023},
abstract = {Both fatty bone marrow (FBM) and somatic mutations in
hematopoietic stem cells (HSCs), also termed clonal
hematopoiesis (CH) accumulate with human aging. However it
remains unclear whether FBM can modify the evolution of CH.
To address this question, we herein present the interaction
between CH and FBM in two preclinical male mouse models:
after sub-lethal irradiation or after castration. An
adipogenesis inhibitor (PPARγ inhibitor) is used in both
models as a control. A significant increase in self-renewal
can be detected in both human and rodent DNMT3AMut-HSCs when
exposed to FBM. DNMT3AMut-HSCs derived from older mice
interacting with FBM have even higher self-renewal in
comparison to DNMT3AMut-HSCs derived from younger mice.
Single cell RNA-sequencing on rodent HSCs after exposing
them to FBM reveal a 6-10 fold increase in DNMT3AMut-HSCs
and an activated inflammatory signaling. Cytokine analysis
of BM fluid and BM derived adipocytes grown in vitro
demonstrates an increased IL-6 levels under FBM conditions.
Anti-IL-6 neutralizing antibodies significantly reduce the
selective advantage of DNMT3AMut-HSCs exposed to FBM.
Overall, paracrine FBM inflammatory signals promote
DNMT3A-driven clonal hematopoiesis, which can be inhibited
by blocking the IL-6 pathway.},
cin = {A350 / B340 / HD01},
ddc = {500},
cid = {I:(DE-He78)A350-20160331 / I:(DE-He78)B340-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37045808},
doi = {10.1038/s41467-023-36906-1},
url = {https://inrepo02.dkfz.de/record/275374},
}