Induced cell-autonomous neutropenia systemically perturbs hematopoiesis in Cebpa enhancer-null mice.

ABSTRACT: The transcription factor C/EBPa initiates the neutrophil gene expression program in the bone marrow (BM). Knockouts of the Cebpa gene or its +37kb enhancer in mice show 2 major findings: (1) neutropenia in BM and blood; (2) decrease in long-term hematopoietic stem cell (LT-HSC) numbers. Whether the latter finding is cell-autonomous (intrinsic) to the LT-HSCs or an extrinsic event exerted on the stem cell compartment remained an open question. Flow cytometric analysis of the Cebpa +37kb enhancer knockout model revealed that the reduction in LT-HSC numbers observed was proportional to the degree of neutropenia. Single-cell transcriptomics of wild-type (WT) mouse BM showed that Cebpa is predominantly expressed in early myeloid-biased progenitors but not in LT-HSCs. These observations suggest

SUBMITTER: Avellino R 

PROVIDER: S-EPMC8905702 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature