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ScRNAseq data of gingival CD11b+ cells from 10% Tet2+/+ BMT and 10% Tet2-/- BMT mice

ABSTRACT: BM cells were isolated from C57BL/6 (CD45.2) Tet2–/– mice and Tet2+/+ littermates, as well as from congenic C57BL/6.SJL (CD45.1) mice (all genotypes purchased from JAX). lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2–/– CD45.2 BM cells and 90% WT CD45.1 BM cells (2x105 Tet2–/– CD45.2 BM cells and 18x105 WT CD45.1 BM cells; total of 2x106 BM cells/recipient mouse). This group was designated ‘10% Tet2–/– BMT’ (experimental). For the control group that was designated ‘10% Tet2+/+ BMT’, lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2+/+ CD45.2 BM cells and 90% WT CD45.1 cells (2x105 Tet2+/+ CD45.2 BM cells & 18x105 WT CD45.1 BM cells, thus exclusively TET2-sufficient cells; total of 2x106 BM cells/recipient mouse). At 12 weeks post-BMT (when there is complete reconstitution of hematopoiesis from transplanted long-term HSCs), ‘10% Tet2–/– BMT’ and ‘10% Tet2+/+ BMT’ mice either received no further treatment (and examined for natural periodontal bone loss) or were subjected to LIP for 5 days.

ORGANISM(S): Mus musculus

PROVIDER: GSE303682 | GEO | 2025/09/08

REPOSITORIES: GEO

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Project description:JAK2V617F is one of the most common mutations in clonal hematopoiesis of indeterminate potential (CHIP) and a major driver of myeloproliferative neoplasms (MPN). To determine the impact of the low frequency JAK2V617F clone on both the hematopoietic system and the bone marrow (BM) stroma, we developed a traceable murine JAK2V617F MPN model where the disease is induced in unconditioned bone marrow transplantation (BMT) recipients. Whole BMT was performed via a single tail vein injection of 5.0x106 cells into unconditioned C57BL/6 Ptprca CD45.1+ recipient mice using CD45.2+ donor cells carrying JAK2V617F isolated from a Poly I:C inducible MPN-like model. BMT resulted in a PV-like phenotype (elevated hematocrit and leukocytosis) with an average donor cell chimerism in peripheral blood of 2.74%. Eight months after BMT, RNA-seq analysis of whole BM sorted according to CD45.1/CD45.2 expression showed significant upregulation of early erythroblast- and myeloid cell-specific transcripts, as well as downregulation of lymphoid transcripts in donor-derived cells compared to controls. Surprisingly, recipient-derived cells also showed upregulation of myeloid- and erythroblast-related transcripts, indicating a skewing of the non-JAK2V617F carrying recipient hematopoietic system towards an MPN-like phenotype. In addition, RNA-seq analysis of the BM stroma from JAK2V617F BMT recipients 28-32 weeks post-BMT indicated significant loss of osteo-mesenchymal transcripts. Consistently, micro-CT imaging indicated loss of trabecular bone. Our model uncovers the impact of JAK2V617F donor cells on the host BM microenvironment and hematopoietic system, driving an MPN phenotype even with low donor cell chimerism within unconditioned recipients. The observation that BMT recipient’s hematopoietic cells, which do not carry JAK2V617F, acquire unique transcriptomic and phenotypic profiles suggests that the MPN clone not only impacts hematopoiesis-supporting stroma but profoundly influences unmutated cells, challenging our current understanding and therapeutic approaches to MPNs and other CHIP-associated diseases.

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ScRNAseq data of gingival CD11b+ cells from 10% Tet2+/+ BMT and 10% Tet2-/- BMT mice

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