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RNA-seq analysis of Jak1 KO and wt LT-HSCs

ABSTRACT: Previous studies have illustrated the importance of Jak1-mediated cytokine signaling in immunological and neoplastic diseases such that JAK1 inhibition is currently being investigated in clinical trials. However, the role of Jak1 in hematopoietic stem cell (HSC) function has not been delineated. Here we show that conditional Jak1 loss in hematopoietic cells reduces HSCs and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient stem cells exhibit decreased competitiveness in vivo, and are unable to rescue hematopoiesis in the setting of myelosuppression. Jak1-deficient HSCs show increased quiescence, an inability to enter the cell cycle in response to hematopoietic stress, and do not respond to type I interferons demonstrating Jak1 as a central node for interferon signaling in HSCs. Moreover, the HSC defect induced by Jak1 loss is not fully rescued by expression of a constitutively active Jak2 allele. Our data highlights an essential role for Jak1 in HSC homeostasis and stress response.

ORGANISM(S): Mus musculus

PROVIDER: GSE85745 | GEO | 2017/12/31

SECONDARY ACCESSION(S): PRJNA339238

REPOSITORIES: GEO

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