PXD050401 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation |
Description | The transcription factor Growth Factor Independence 1B (GFI1B) recruits Lysine Specific Demethylase 1A (LSD1/KDM1A) to stimulate gene programs relevant for megakaryocyte and platelet biology. Inherited pathogenic GFI1B variants result in thrombocytopenia and bleeding propensities with varying intensity. Whether these affect similar gene programs is unknow. Here we studied transcriptomic effects of four patient-derived GFI1B variants (GFI1BT174N,H181Y,R184P,Q287*) in MEG01 megakaryoblasts. Compared to normal GFI1B, each variant affected different gene programs with GFI1BQ287* uniquely failing to repress myeloid traits. In line with this, single cell RNA-sequencing of induced pluripotent stem cell (iPSC)-derived megakaryocytes revealed a 4.5-fold decrease in the megakaryocyte/myeloid cell ratio in GFI1BQ287* versus normal conditions. Inhibiting the GFI1B-LSD1 interaction with small molecule GSK-LSD1 resulted in activation of myeloid genes in normal iPSC-derived megakaryocytes similar as observed for GFI1BQ287* iPSC-derived megakaryocytes. Thus, GFI1B and LSD1 facilitate gene programs relevant for megakaryopoiesis while simultaneously repressing programs that induce myeloid differentiation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:34:46.275.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Pascal Jansen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-03-06 04:51:37 | ID requested | |
1 | 2024-03-28 08:15:52 | announced | |
⏵ 2 | 2024-10-22 06:34:46 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, KDM1A, CRISpaint, GFI1B |
Contact List
Bert A. van der Reijden |
contact affiliation | Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Research Institute for Medical Innovation, Nijmegen, The Netherlands. |
contact email | Bert.vanderReijden@radboudumc.nl |
lab head | |
Pascal Jansen |
contact affiliation | Radboud University |
contact email | p.jansen@science.ru.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050401
- Label: PRIDE project
- Name: GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation