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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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)
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| 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 |
| Citation missing |
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| Submission date |
Jun 15, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Martin Wahlestedt |
| E-mail(s) |
martin.wahlestedt@med.lu.se
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| Organization name |
Lund University
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| Department |
Divison of Molecular Hematology
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| Street address |
Klinikgatan 26
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| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| 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 |
| GSM1711436 |
Hlf inducible GMLPs cultured on OP9 stroma with doxycycline, Replicate 2 |
| GSM1711437 |
Control lentivirus transduced GMLPs cultured on OP9 stroma, Replicate 1 |
| GSM1711438 |
Control lentivirus transduced GMLPs cultured on OP9 stroma, Replicate 2 |
| GSM1711439 |
Hlf/Hlf forced dimer lentivirus transduced GMLPs cultured on OP9 stroma, Replicate 1 |
| GSM1711440 |
Hlf/Hlf forced dimer lentivirus transduced GMLPs cultured on OP9 stroma, Replicate 2 |
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| Relations |
| BioProject |
PRJNA286986 |
| SRA |
SRP059485 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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