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| Status |
Public on Feb 09, 2013 |
| Title |
The role of Ldb1 in hemangioblast development: genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis (sequencing) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
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| Overall design |
Examination of endogenous Ldb1 genome-wide binding sites comparsion between ChIP and Control on Flk1+ BL-CFCs
RNA was isolated from Ldb1+/+ and Ldb1-/- Flk1+ cells with the QIAGEN RNeasy Mini Kit and integrity was checked on the Agilent 2100 Bioanalyzer. RNA sequencing was performed on Illumina HiSeq 2000 platform according to the manufacturer instructions.
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| Contributor(s) |
Mylona A, Andrieu-Soler C, Thongjuea S, Martella A, Soler E, Jorna R, Hou J, Kockx C, van Ijcken W, Lenhard B, Grosveld F |
| Citation(s) |
23390196 |
| |
| Submission date |
Dec 19, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Supat Thongjuea |
| E-mail(s) |
supat.thongjuea@ndcls.ox.ac.uk
|
| Organization name |
The Weatherall Institute of Molecular Medicine
|
| Department |
MRC Molecular Haematology Unit
|
| Street address |
Headington
|
| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE43044 |
The role of Ldb1 in hemangioblast development: genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis |
|
| Relations |
| BioProject |
PRJNA184174 |
| SRA |
SRP017620 |
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