RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity

Sonia Cellot, Kristin Hope, Jalila Chagraoui, Martin Sauvageau, Eric Deneault, Tara MacRae, Nadine Mayotte, Brian T Wilhelm, Josette R Landry, Stephen Bek Ngie Ting, Jana Krosl, Keith Humphries, Alexander Thompson, Guy Sauvageau

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    43 Citations (Scopus)

    Abstract

    Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain?containing family of demethylases comprises 27 members that target mono-, di-, and trimethylated lysine residues of histone (or nonhistone) proteins. To evaluate their role in regulation of hematopoietic stem cell (HSC) behavior, we performed an in vivo RNAi-based functional screen and demonstrated that Jarid1b and Jhdm1f play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSCs with preserved long-term in vivo lymphomyeloid differentiation potential. Through RNA sequencing analysis, Jarid1b knockdown was associated with increased expression levels of several HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) and reduced levels of differentiation-associated genes. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative regulator of HSC activity and Jhdmlf as a positive regulator of HSC activity.
    Original languageEnglish
    Pages (from-to)1545 - 1555
    Number of pages11
    JournalBlood
    Volume122
    Issue number9
    DOIs
    Publication statusPublished - 2013

    Cite this

    Cellot, S., Hope, K., Chagraoui, J., Sauvageau, M., Deneault, E., MacRae, T., Mayotte, N., Wilhelm, B. T., Landry, J. R., Ting, S. B. N., Krosl, J., Humphries, K., Thompson, A., & Sauvageau, G. (2013). RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity. Blood, 122(9), 1545 - 1555. https://doi.org/10.1182/blood-2013-04-496281