The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [high-throughput sequencing]

We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects. Overall design: High-troughput RNA-sequencing of sorted HSC (Lin-Sca+Kit+CD48-CD150+) from wild type or Huwe1 conditional knockout mice (constitutively deleted with Vav-Cre recombinase or inducibly deleted with Mx1-Cre)

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King B, Boccalatte F, Moran-Crusio K, Wolf E, Wang J, Kayembe C, Lazaris C, Yu X, Aranda-Orgilles B, Lasorella A, Aifantis I