Journal Article

DKFZ-2023-00740

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis.

Zioni, N. ; Bercovich, A. A. ; Chapal-Ilani, N. ; Bacharach, T. ; Rappoport, N. ; Solomon, A. ; Avraham, R. ; Kopitman, E. ; Porat, Z. ; Sacma, M. ; Hartmut, G. ; Scheller, M. ; Müller-Tidow, C.DKFZ* ; Lipka, D.DKFZ* ; Shlush, E. ; Minden, M. ; Kaushansky, N. ; Shlush, L. I.

2023
Nature Publishing Group UK [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-023-36906-1

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.

---

Contributing Institute(s):

1. A350 Reguläre Mechanismen der Genexpression (A350)
2. Translationale Medizinische Onkologie (B340)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---