Clonal hematopoiesis of indeterminate potential (CHIP) is linked to systemic inflammation and increased malignant risk, yet its impact on the bone marrow (BM) niche remains poorly understood. Through single-cell transcriptomic profiling of freshly isolated BM, we identify fibro-inflammatory rewiring as an early hallmark of CHIP. Beyond a myeloid-biased inflammatory state, CHIP BM exhibited coordinated TNFα activation across hematopoietic progenitor, monocyte, and stromal compartments. Stromal populations displayed early fibrotic remodeling, with mesenchymal and vascular cells upregulating collagen and extracellular matrix programs. Fibroblasts were markedly expanded independent of mutational subtype and acquired cancer-associated fibroblast (CAF)-like programs, rewiring niche interactions through IL-6, TGFβ, and collagen-integrin signaling. Together, these findings establish fibro-inflammatory BM remodeling as an early hallmark of clonal expansion, linking CHIP to prefibrotic stromal remodeling, immune dysregulation, and a niche architecture consistent with increased malignant risk.
This dataset includes raw single cell RNA sequencing data from 13 pMMR colon cancer patients treated with neoadjuvant immune checkpoint blockade in the NICHE trial. This dataset comprises pre-treatment colon cancer biopsy samples, which digested to obtain single cell suspensions, sorted for CD45+, labelled with hashtag antibodies, split in 3 cell pools, and distributed in 5 sequencing samples (7654_1-5). 30 FASTQ files were generated, 10 files for scRNAseq gene expression (10X Genomics Chromium Next GEM Single Cell 5' v2), 10 files for single cell TCRseq (10X Genomics Chromium Next GEM Single Cell V(D)J Reagent Kits 5' v2) and 10 files for feature barcodes and hashtag antibodies, with feature reference barcodes provided. Samples were sequenced on Illumina Novaseq 6000 and raw FASTQ files were later processed with Cellranger workflows from 10X Genomics, investigating features of pre-treatment immune tumour cells and associations with neoadjuvant response.
