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Hepatic Leukemia Factor maintains quiescence of hematopoietic stem cells and protects the stem cell pool during regeneration

ABSTRACT: The transcription factor hepatic leukemia factor (HLF) is highly expressed in hematopoietic stem cells (HSCs) and has been proposed to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function has remained unknown. Here we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters. By contrast, when challenged through transplantation, Hlf deficient HSCs demonstrate an impaired ability to reconstitute hematopoiesis and gradually exhaust upon serial transplantation. Transcriptional profiling displayed changes associated with cellular activation in Hlf deficient HSCs, and cell cycle analysis showed a significant reduction of dormant HSCs. Accordingly, Hlf deficient mice were hypersensitive to toxic insults targeting dividing cells that completely eradicated the HSC pool. In summary, our findings unravel a novel role for HLF as a critical regulator of HSC quiescence and as an essential factor to maintain the HSC pool during regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE100385 | GEO | 2017/12/18

SECONDARY ACCESSION(S): PRJNA391494

REPOSITORIES: GEO

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