Clonal hematopoiesis of indeterminate potential (CHIP) and myelodysplastic syndromes (MDS) are disorders associated with clonal expansion within the hematopoietic system that can result in cytopenias, increased risk of cardiovascular and autoimmune disease and progression to acute myeloid leukemia (AML). Multiple recent investigations into hematopoietic malignancies such as multiple myeloma (MM) and AML leveraging single-cell transcriptomics to investigate the tissue at cellular resolution have highlighted the importance of the bone marrow microenvironment in creating favorable conditions for mutant cells and promoting disease progression and relapse. However a detailed understanding of how various bone marrow niches are perturbed in CHIP and MDS is missing. An ancillary, but important technical question related to single-cell profiling of cancer tissues is accurate discrimination of mutant cells from their non-malignant counterparts. This is not always straightforward, particularly in the context of blood cancers, because of a lack of definitive features between the two on the level of RNA expression or cell surface markers. The aim of this thesis is to provide a detailed characterization of how the bone marrow niche is affected in CHIP and MDS and how these alterations might contribute to pathogenesis of these conditions. We first describe SpliceUp, a novel computational method for identifying cells with mutations in splicing factor genes, which is a common feature of various blood cancers, including MDS, in single-cell transcriptomic data. Next we provide a detailed bone marrow niche characterization of healthy controls, CHIP and MDS patients using a combination of bulk and single-cell transcriptomics, proteomics, cell sorting and imaging techniques. We highlight several important features associated with inflammatory changes in the bone marrow in CHIP and MDS, such as alteration in stromal and T cell composition and emergence of inflammatory MSCs (iMSCs) and IFN-response T cells restricted to the disease conditions. Our findings indicate a set of common inflammatory changes in the niche partially overlapping with existing findings in AML and MM, as well as certain unique features like residual expression of HSPC-support genes in iMSC specific to our MDS samples. This work provides a general characterization of the bone marrow microenvironment in CHIP and MDS and puts it in the context of existing knowledge about other hematological malignancies. It highlights the importance of the bone marrow niche in these disorders and provides a reference for future studies targeting the individual components of this niche.