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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 27, 2020 |
| Title |
HES1 and HES4 have both unique and overlapping roles as downstream mediators of Notch-dependent hematopoietic lineage decisions in human |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In both mouse and human, Notch1 activation is the main initial driver to induce T-cell development in hematopoietic progenitor cells. The initiation of this developmental process coincides with Notch1-dependent repression of differentiation towards other hematopoietic lineages. Although well described in mice, the role of the individual Notch1 target genes during these hematopoietic developmental choices is still unclear in human. Here, we investigated the functional capacity of the Notch1 target genes HES1 and HES4 to modulate human Notch1-dependent hematopoietic lineage decisions. Using well-established in vitro cocultures and RNA sequencing, we show that HES1 acts as a repressor of differentiation by maintaining a quiescent stem cell signature in CD34+ hematopoietic progenitor cells. While HES4 can also inhibit NK and myeloid development like HES1, it acts differently on the T- versus B-cell lineage choice. Surprisingly, HES4 is not capable of repressing B-cell development, the most sensitive hematopoietic lineage with respect to Notch-mediated repression. In contrast to HES1, HES4 promotes initiation of early T-cell development. Overall, we show that the Notch1 target genes HES1 and HES4 display both unique and overlapping functions downstream of Notch during human hematopoietic lineage decisions.
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| Overall design |
Three independent CB CD34+Lin- samples, from three independent donors, were transduced with a control-, HES1- or HES4-expressing construct and cultured for one day on OP9-GFP or OP9-DLL1 before extracting RNA and sequencing.
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| Contributor(s) |
De Decker M, Taghon T |
| Citation(s) |
31919081 |
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| Submission date |
May 02, 2019 |
| Last update date |
Jul 27, 2020 |
| Contact name |
Matthias De Decker |
| E-mail(s) |
[email protected]
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| Organization name |
Ghent University
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| Department |
Diagnostic Sciences
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| Lab |
Immunology
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| Street address |
Corneel Heymanslaan 10
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| City |
Ghent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| GSM3744890 |
cord blood CD34+, OP9-GFP_HES4_1 |
| GSM3744891 |
cord blood CD34+, OP9-GFP_HES4_2 |
| GSM3744892 |
cord blood CD34+, OP9-GFP_HES4_3 |
| GSM3744893 |
cord blood CD34+, OP9-GFP_HES1_1 |
| GSM3744894 |
cord blood CD34+, OP9-GFP_HES1_2 |
| GSM3744895 |
cord blood CD34+, OP9-GFP_HES1_3 |
| GSM3744896 |
cord blood CD34+, OP9-DLL1_Ctrl_1 |
| GSM3744897 |
cord blood CD34+, OP9-DLL1_Ctrl_2 |
| GSM3744898 |
cord blood CD34+, OP9-DLL1_Ctrl_3 |
| GSM3744899 |
cord blood CD34+, OP9-DLL1_HES4_1 |
| GSM3744900 |
cord blood CD34+, OP9-DLL1_HES4_2 |
| GSM3744901 |
cord blood CD34+, OP9-DLL1_HES4_3 |
| GSM3744902 |
cord blood CD34+, OP9-DLL1_HES1_1 |
| GSM3744903 |
cord blood CD34+, OP9-DLL1_HES1_2 |
| GSM3744904 |
cord blood CD34+, OP9-DLL1_HES1_3 |
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| Relations |
| BioProject |
PRJNA540777 |
| SRA |
SRP194524 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130614_DESeq2_normalized_reads.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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