PXD050401-1

PXD050401 is an original dataset announced via ProteomeXchange.

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	2024-03-28
AnnouncementXML	Submission_2024-03-28_08:15:52.473.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

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.

Dataset with its publication pending

submitter keyword: Human, KDM1A, CRISpaint, GFI1B

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

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PRIDE project URI

• PRIDE
  1. PXD050401
     1. Label: PRIDE project
     2. Name: GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation