Low-input proteomics identifies vWF as a negative regulator of Tet2 mutant hematopoietic stem cell expansion.

ABSTRACT: Despite rapid advances in mapping genetic drivers and gene expression changes in hematopoietic stem cells (HSCs), few studies exist at the protein level. We perform a deep, multi-omics characterization (epigenome, transcriptome, and proteome) of HSCs in a mouse model carrying a loss-of-function mutation in Tet2, a driver of increased self-renewal in blood cancers. Using state-of-the-art, multiplexed, low-input mass spectrometry (MS)-based proteomics, we profile TET2-deficient (Tet2^-/-) HSCs, revealing previously unrecognized molecular processes that define the pre-leukemic HSC molecular landscape. Specifically, we obtain more accurate stratification of wild-type and Tet2^-/- HSCs than transcriptomic approaches and identify extracellular matrix (ECM) molecules as being

SUBMITTER: Jassinskaja M 

PROVIDER: S-EPMC12847853 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature