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Series GSE69858 Query DataSets for GSE69858
Status Public on Jun 12, 2016
Title Critical modulation of hematopoietic lineage fate by Hepatic Leukemia Factor
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor Hepatic Leukemia Factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its’ normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates. Reciprocally, we observed rapid lymphoid commitment upon reduced Hlf activity. The arising phenotypes resulted from Hlf-binding to active enhancers of myeloid-competent cells, transcriptional induction of myeloid and ablation of lymphoid gene programs, with Hlf induction of Nuclear Factor I C (Nfic) as a functionally relevant target gene. Thereby, our studies establish Hlf as a key regulator of the earliest lineage-commitment events at the transition from multipotency to lineage-restricted progeny, with implications for both normal and malignant hematopoiesis.
Overall design Gene expression profiling of control or Hlf/Hlf lentivirus infected GMLPs (2 replicates per group) and Hlf inducible GMLPs maintained for 4 days on OP9 stroma in the presence or absence of doxycycline (2 replicates per group)
Contributor(s) Wahlestedt M, Ladopoulos V, Hidalgo I, Sanchez Castillo M, Hannah R, Säwén P, Wan H, Dudenhöffer-Pfeifer M, Magnusson M, Norddahl GL, Göttgens B, Bryder D
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Submission date Jun 15, 2015
Last update date May 15, 2019
Contact name Martin Wahlestedt
Organization name Lund University
Department Divison of Molecular Hematology
Street address Klinikgatan 26
City Lund
ZIP/Postal code 22184
Country Sweden
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM1711433 Hlf inducible GMLPs cultured on OP9 stroma without doxycycline, Replicate 1
GSM1711434 Hlf inducible GMLPs cultured on OP9 stroma without doxycycline, Replicate 2
GSM1711435 Hlf inducible GMLPs cultured on OP9 stroma with doxycycline, Replicate 1
BioProject PRJNA286986
SRA SRP059485

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Supplementary file Size Download File type/resource
GSE69858_Control_virus_vs_HlfHlf_virus_edgeR.txt.gz 29.4 Kb (ftp)(http) TXT
GSE69858_no_dox_vs_DOX_edgeR.txt.gz 157.2 Kb (ftp)(http) TXT
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Processed data are available on Series record

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