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| Status |
Public on Nov 25, 2021 |
| Title |
Depicting human endothelial to hematopoietic transition and the effects of modulating pyruvate catabolism on blood formation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hematopoietic stem cell (HSC) quiescence, maintenance and differentiation are closely linked to changes in metabolism. However, the role of metabolism during the first emergence of HSCs from hemogenic endothelium (HE) is still unknown. In this study, we focus on the implication of energetic metabolic pathways during endothelial to hematopoietic transition (EHT). EHT is accompanied by a metabolic switch, with concomitant increases in glycolysis and oxidative phosphorylation (OXPHOS). Inhibiting glycolysis in HE cells leads to a block in hematopoietic lineage specification. An OXPHOS fuel, glutamine, is essential for HSC emergence and provides distinct intermediates to mediate differentiation towards the two major hematopoietic lineages, GPA+ and CD45+ cells. Strikingly, shifting the fate of pyruvate from glycolysis to the TCA cycle redirects HE specification towards CD45+ cells at the expense of GPA+ cells and vice versa. As such, our findings reveal the plasticity of hematopoietic lineage specification during EHT which can be modulated by metabolism.
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| Overall design |
Transcriptomic analysis of hiPSC-derived HE, EHT, HSC-like cells and cord blood CD34+ cells. Comparison of control HE cells with UK5099- or DCA-treated HE cells.
***Raw data not provided due to patient privacy concerns***
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| Contributor(s) |
Mansell E, Canals I, Guibentif C, Soneji S, Woods N, Oburoglu L |
| Citation(s) |
34914165 |
| Submission date |
Nov 29, 2019 |
| Last update date |
Feb 18, 2022 |
| Contact name |
Shamit Soneji |
| Organization name |
BMC
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| Street address |
Solvegatan 19
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| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA592550 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141189_RAW.tar |
90.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Raw data not provided for this record |
| Processed data provided as supplementary file |
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