Thrombopoietin protects hematopoietic stem cells from retrotransposon-mediated damage by promoting an antiviral response.

ABSTRACT: Maintenance of genomic integrity is crucial for the preservation of hematopoietic stem cell (HSC) potential. Retrotransposons, spreading in the genome through an RNA intermediate, have been associated with loss of self-renewal, aging, and DNA damage. However, their role in HSCs has not been addressed. Here, we show that mouse HSCs express various retroelements (REs), including long interspersed element-1 (L1) recent family members that further increase upon irradiation. Using mice expressing an engineered human L1 retrotransposition reporter cassette and reverse transcription inhibitors, we demonstrate that L1 retransposition occurs in vivo and is involved in irradiation-induced persistent γH2AX foci and HSC loss of function. Thus, RE represents an important intrinsic HSC threat. Furthermo

SUBMITTER: Barbieri D 

PROVIDER: S-EPMC5940259 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature