Transcriptomics

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Expression data from B220+ Hspa9+/+ and Hspa9+/- CFU-PreB colonies isolated on Day 7 of culture


ABSTRACT: CFU-PreB colonies are reduced in number and size in Hspa9+/- mice compared to wildtype littermates. We compared the expression profiles of these colonies to gain insight into the mechanism driving this difference. HSPA9 is located on chromosome 5q31.2 in humans, a region that is commonly deleted in patients with myeloid malignancies [del(5q)], including myelodysplastic syndromes (MDS). HSPA9 expression is reduced by 50% in patients with del(5q)-associated MDS, consistent with haploinsufficient levels. Zebrafish mutants and knockdown studies in human and mouse cells have implicated a role for HSPA9 in hematopoiesis. To comprehensively evaluate the effects of Hspa9 haploinsufficiency on hematopoiesis, we generated an Hspa9 knockout mouse model. While homozygous knockout of Hspa9 is embryonic lethal, mice with heterozygous deletion of Hspa9 (Hspa9+/-) are viable and have a 50% reduction in Hspa9 expression. Hspa9+/- mice have normal basal hematopoiesis and do not develop MDS. However, Hspa9+/- mice have a cell-intrinsic reduction in bone marrow CFU-PreB colony formation without alterations in the number of B-cell progenitors in vivo, consistent with a functional defect in Hspa9+/- B-cell progenitors. We further reduced Hspa9 expression (<50%) using RNAi and observe reduced B-cell progenitors in vivo, indicating that appropriate levels (≥50%) of Hspa9 are required for normal B-lymphopoiesis in vivo. Knockdown of Hspa9 in an IL-7 dependent mouse B-cell line reduced Stat5 phosphorylation following IL-7 receptor stimulation, supporting a role for Hspa9 in Stat5 signaling in B-cells. Collectively, these data implicate a role for Hspa9 in B-lymphopoiesis and Stat5 activation downstream of IL-7 signaling. Bone marrow cells from 5 Hspa9+/+ and 5 Hspa9+/- mice were independently cultured in CFU-PreB methylcellulose medium for 7 days. PreB colonies were isolated and B220+ cells were flow sorted for RNA isolation.

ORGANISM(S): Mus musculus  

SUBMITTER: Jin Shao   Matthew Ndonwi  Matt Walter  Tuoen Liu  Kilannin Krysiak  Matthew J Walter  Justin F Tibbitts 

PROVIDER: E-GEOD-65588 | ArrayExpress | 2015-02-04

SECONDARY ACCESSION(S): GSE65588PRJNA274441

REPOSITORIES: GEO, ArrayExpress

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