Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration | Zendy

Karolina Komorowska | Zendy; Alexander Doyle | Zendy; Martin Wahlestedt | Zendy; Agatheeswaran Subramaniam | Zendy; Shubhranshu Debnath | Zendy; Jun Chen | Zendy; Shamit Soneji | Zendy; Ben Van Handel | Zendy; Hanna Mikkola | Zendy; Kenichi Miharada | Zendy; David Bryder | Zendy; Jonas Larsson | Zendy; Mattias Magnusson | Zendy

Open Access

Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration

Author(s) -

Karolina Komorowska,

Alexander Doyle,

Martin Wahlestedt,

Agatheeswaran Subramaniam,

Shubhranshu Debnath,

Jun Chen,

Shamit Soneji,

Ben Van Handel,

Hanna Mikkola,

Kenichi Miharada,

David Bryder,

Jonas Larsson,

Mattias Magnusson

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.11.084

Subject(s) - haematopoiesis , stem cell , biology , microbiology and biotechnology , hematopoietic stem cell , transplantation , transcription factor , stem cell factor , regulator , regeneration (biology) , cancer research , leukemia , immunology , genetics , medicine , gene

The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters, including an intact HSC pool during steady-state hematopoiesis. In contrast, when challenged through transplantation, Hlf-deficient HSCs showed an impaired ability to reconstitute hematopoiesis and became gradually exhausted upon serial transplantation. Transcriptional profiling of Hlf-deficient HSCs revealed changes associated with enhanced cellular activation, and cell-cycle analysis demonstrated a significant reduction of quiescent HSCs. Accordingly, toxic insults targeting dividing cells completely eradicated the HSC pool in Hlf-deficient mice. In summary, our findings point to HLF as a critical regulator of HSC quiescence and as an essential factor for maintaining the HSC pool during regeneration.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research