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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 11, 2016 |
| Title |
Critical modulation of hematopoietic lineage fate by the PAR/bZIP transcription factor Hepatic Leukemia Factor |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Blood cell formation is a tightly regulated process initiated from a rare population of multipotent hematopoietic stem cells. Subsequent differentiation proceeds in a hierarchical manner with the generation of intermediate progenitor cells, in which alternative lineage potentials become gradually restricted. A deeper understanding of these events is crucial not only to understand normal blood cell formation, but also for leukemia, where a defining feature is inappropriate differentiation. Here, we identified Hepatic Leukemia Factor (Hlf) as being highly and selectively expressed in primitive multipotent hematopoietic stem and progenitors. We demonstrate that Hlf is a strong negative regulator of B-, NK- and T cell development and instructs multipotent progenitors to adopt a myeloid fate in a cell autonomous manner; phenotypes underwritten by the induction of myeloid affiliated transcriptional programs, the concomitant ablation of lymphoid gene programs and genome-wide binding spectra that involved active enhancers of myeloid-competent cells. Collectively, 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 |
Identification of Hlf binding sites in Lin-Sca-1+c-Kit+ cells
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| Contributor(s) |
Wahlestedt M, Ladopoulos V, Säwén P, Magnusson M, Norddahl GL, Castillo MS, Hannah RL, Göttgens B, Bryder D |
| Citation(s) |
29166614 |
| Submission date |
Jun 12, 2015 |
| Last update date |
May 06, 2020 |
| Contact name |
Evangelia Diamanti |
| E-mail(s) |
ed347@cam.ac.uk
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| Phone |
01223 62317
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| Organization name |
University of Cambridge
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| Department |
Haematology
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| Lab |
Gottgens
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| Street address |
Wellcome Trust / MRC Building, Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA286862 |
| SRA |
SRP059428 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69817_RAW.tar |
443.3 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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