Chromatin accessibility in stem cells unveils progressive transcriptional alterations in myelodysplastic syndrome.

ABSTRACT: Myelodysplastic syndrome (MDS) originates from hematopoietic stem cell (HSC) clones with acquired gene mutations. However, the molecular characteristics of MDS stem cells remain poorly understood. Here, we show that the chromatin accessibility profiles of MDS stem cells more accurately reflect disease status than those of progenitor cells and reveal the process of stem cell alterations during disease progression. Characterization of differentially accessible regions (DARs) shows that MDS stem cells acquire progenitor-like chromatin accessibility during disease progression, leading to disruption of the normal stem-progenitor hierarchy. Profiling of transcription factor-binding motifs at DARs further uncovers precocious activation of myeloid transcriptional networks in MDS stem cells, with a

SUBMITTER: Oshima M 

PROVIDER: S-EPMC12663188 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature