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Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (NOD/SCID/IL-2Rgc-null subset)

ABSTRACT: Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (NOD/SCID/IL-2Rgc-null subset)

PROVIDER: PRJEB59816 | ENA |

REPOSITORIES: ENA

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Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (NOD/SCID/IL-2Rgc-null subset)

Project description:Accumulation of fatty bone marrow (FBM) is one of the key age related changes possibly influencing the blood system. While a link between obesity and cancer evolution has been reported it remains unknown whether FBM can modify the evolution of the early stages of leukemia and clonal hematopoiesis (CH). To address this question, we established different FBM mouse models in immunodeficient mice in whom we can study both mouse and human cells. We focused our studies on two FBM models: 1) after sublethal irradiation; 2) after castration; and in both we used an adipogenesis inhibitor as a control (PPARγ inhibitor). We transplanted both human and mice hematopoietic stem cells (HSCs) carrying DNMT3A mutations into immunodeficient mice with FBM. A significant increase in self-renewal was found when DNMT3AMut-HSCs were exposed to FBM. To better understand the mechanisms of the FBM-CH interaction, we performed single cell RNA-sequencing on HSPCs after FBM exposure in vivo. A 6-10 fold increase in DNMT3AMut-HSCs was observed under FBM conditions in comparison to normal bone marrow. Mutated HSCs from mice exposed to FBM exhibited an activated inflammatory signaling (IL-6 and IFNγ). Cytokine analysis of BM fluid and BM derived adipocytes grown in vitro demonstrated increased IL-6 levels under FBM conditions. Anti-IL-6 neutralizing antibodies significantly reduced the selective advantage of mice derived DNMT3AMut-HSCs exposed to FBM. Overall, paracrine FBM inflammatory signals promote DNMT3A-driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 receptor.

2023-02-19 | E-MTAB-12620 | biostudies-arrayexpress

Expression data from NOD-scid vs B6-scid pancreas, submandibular glands, & lacrimal glands

Project description:Prior to the onset of autoimmune destruction, type 1 diabetic patients and an animal model thereof, the nonobese diabetic (NOD) mouse, show morphological and functional abnormalities in target organs, which may act as inciting events for leukocyte infiltration. To better understand these abnormalities, but without the complications associated with inflammatory infiltrates, we examined genes expressed in autoimmune target tissues (pancreas, submandibular glands, and lacrimal glands) of NOD/scid mice and of autoimmune-resistant C57BL6/scid mice. Keywords: tissue expression, disease prone versus resistant strain comparison

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Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (Dnmt3A KI heterozygote subset)

Project description:Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (Dnmt3A KI heterozygote subset)

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Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (wt/DNMT3A KI subset)

Project description:Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (wt/DNMT3A KI subset)

| PRJEB59818 | ENA

Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (wt/DNMT3A KI subset)

2023-02-19 | E-MTAB-12614 | biostudies-arrayexpress

Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (Dnmt3A KI heterozygote subset)

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Single-cell RNA sequencing of BCSCs from solid tumors taken from NOD/SCID mice

Project description:We report the single-cell transcriptome of breast cancer stem cells (BCSCs) from solid tumors taken from NOD/SCID mice.

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Transcription profiling of pancreata, submandibular, and lacrimal glands from NOD-scid and C57Bl/6-scid mice to study the gene expression patterns of nonobese diabetic mice.

Project description:Prior to the onset of autoimmune destruction, type 1 diabetic patients and an animal model thereof, the nonobese diabetic (NOD) mouse, show morphological and functional abnormalities in target organs, which may act as inciting events for leukocyte infiltration. To better understand these abnormalities, but without the complications associated with inflammatory infiltrates, we examined genes expressed in autoimmune target tissues (pancreas, submandibular glands, and lacrimal glands) of NOD/scid mice and of autoimmune-resistant C57BL6/scid mice. Experiment Overall Design: Pancreata (6 weeks old mice), submandibular (9 and 15 weeks), and lacrimal glands (15 weeks) from individual NOD-scid and B6-scid mice were isolated for RNA extraction and hybridization on Affymetrix microarrays.

2007-11-29 | E-GEOD-4953 | biostudies-arrayexpress

Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis.

Project description: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.

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scRNAseq of islets extracted from NOD-SCID mice shows no evidence for non-endocrine origin of regenerated beta cells

Project description:Single cell RNA sequencing was performed on adult NOD-SCID mice to identify the various cell types in the pancreatic islets of Langerhans

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