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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 10, 2022 |
| Title |
Synergistic activation of RARb and RARg-driven programs restores cell-types specialization during stem cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
How cells respond to different external cues to develop along defined cell lineages composing complex tissues is a major question in systems biology. In this study, we studied the role of synthetic agonists targeting specific Retinoic acid receptors (RARs) on activating major gene regulatory wires driving cell specialization during nervous tissue formation issued from P19 stem cells. Specifically, we have revealed that the synergistic activation of the RAR and RAR nuclear receptors by their cognate ligands (BMS641 or BMS961) induce neuronal maturation, inlcuding specialized neuronal subtypes as well as to astrocytes and oligodendrocyte precursors.
With the help of Rar-null mutant lines, combined with the use of RAR-specific agonists, global transcriptome mapping and an in-silico modeling of transcription regulatory signalling propagation, we have highlighted major gene programs essential for optimal neuronal cell specialization. Overall, this study provides a systems biology view of the gene programs behind the previously observed redundancy between RAR receptors, paving the way for their potential use for directing cell specialization during nervous tissue formation.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for WT P19 or rar-null mutant EC cells treated with ATRA, BMS753, BMS641, BMS961 or a combination of BMS641 & BMS961 .
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| Contributor(s) |
Koshy A, Mathieux E, Stüder F, Bramoulle A, Lieb M, Colombo BM, Gronemeyer H, Mendoza-Parra MA |
| Citation(s) |
36446525 |
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| Submission date |
May 25, 2022 |
| Last update date |
Dec 15, 2022 |
| Contact name |
Marco Antonio Mendoza Parra |
| E-mail(s) |
mmendoza@genoscope.cns.fr
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| Organization name |
Genoscope
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| Street address |
2 Gaston Crémieux
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| City |
Evry |
| ZIP/Postal code |
91000 |
| Country |
France |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| GSM6195541 |
P19, WT, BMS753, Day 2 |
| GSM6195542 |
P19, WT, BMS753, Day 4 |
| GSM6195543 |
P19, WT, BMS753, Day 10 |
| GSM6195544 |
P19, WT, BMS641+BMS961, Day 2 |
| GSM6195545 |
P19, WT, BMS641+BMS961, Day 4 |
| GSM6195546 |
P19, WT, BMS641+BMS961, Day 10 |
| GSM6195547 |
P19, WT, EtOH, Day 2 |
| GSM6195548 |
P19, WT, EtOH, Day 4 |
| GSM6195549 |
P19, WT, EtOH, Day 10 |
| GSM6195550 |
P19, WT, BMS961, Day 10 |
| GSM6195551 |
P19, raraKO, ATRA, Day 10 |
| GSM6195552 |
P19, raraKO, BMS961, Day 10 |
| GSM6195553 |
P19, raraKO, BMS641+BMS961, Day 10 |
| GSM6195554 |
P19, rarbKO, ATRA, Day 10 |
| GSM6195555 |
P19, rarbKO, BMS753, Day 10 |
| GSM6195556 |
P19, rarbKO, BMS961, Day 10 |
| GSM6195557 |
P19, rarbKO, BMS641+BMS961, Day 10 |
| GSM6195558 |
P19, rargKO, ATRA, Day 10 |
| GSM6195559 |
P19, rargKO, BMS753, Day 10 |
| GSM6195560 |
P19, rargKO, BMS641, Day 10 |
| GSM6195561 |
P19, rargKO, BMS641+BMS961, Day 10 |
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| Relations |
| BioProject |
PRJNA842391 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE204816_RAW.tar |
140.0 Kb |
(http)(custom) |
TAR (of CSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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