PUBLICATION
Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis
- Authors
- Dobrzycki, T., Mahony, C.B., Krecsmarik, M., Koyunlar, C., Rispoli, R., Peulen-Zink, J., Gussinklo, K., Fedlaoui, B., de Pater, E., Patient, R., Monteiro, R.
- ID
- ZDB-PUB-200216-4
- Date
- 2020
- Source
- Communications biology 3: 71 (Journal)
- Registered Authors
- Mahony, Christopher, Monteiro, Rui, Patient, Roger K.
- Keywords
- none
- Datasets
- GEO:GSE143763
- MeSH Terms
-
- Age Factors
- Animals
- Base Sequence
- Cellular Reprogramming/genetics*
- Chromatin/genetics
- Conserved Sequence*
- Endothelium/metabolism*
- Enhancer Elements, Genetic*
- GATA2 Transcription Factor/genetics*
- Gene Expression Regulation, Developmental
- Genes, Reporter
- Genetic Loci
- Hematopoiesis/genetics*
- Hematopoietic Stem Cells/metabolism
- Sequence Deletion*
- Zebrafish
- PubMed
- 32054973 Full text @ Commun Biol
Citation
Dobrzycki, T., Mahony, C.B., Krecsmarik, M., Koyunlar, C., Rispoli, R., Peulen-Zink, J., Gussinklo, K., Fedlaoui, B., de Pater, E., Patient, R., Monteiro, R. (2020) Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis. Communications biology. 3:71.
Abstract
Gata2 is a key transcription factor required to generate Haematopoietic Stem and Progenitor Cells (HSPCs) from haemogenic endothelium (HE); misexpression of Gata2 leads to haematopoietic disorders. Here we deleted a conserved enhancer (i4 enhancer) driving pan-endothelial expression of the zebrafish gata2a and showed that Gata2a is required for HE programming by regulating expression of runx1 and of the second Gata2 orthologue, gata2b. By 5 days, homozygous gata2aΔi4/Δi4 larvae showed normal numbers of HSPCs, a recovery mediated by Notch signalling driving gata2b and runx1 expression in HE. However, gata2aΔi4/Δi4 adults showed oedema, susceptibility to infections and marrow hypo-cellularity, consistent with bone marrow failure found in GATA2 deficiency syndromes. Thus, gata2a expression driven by the i4 enhancer is required for correct HE programming in embryos and maintenance of steady-state haematopoietic stem cell output in the adult. These enhancer mutants will be useful in exploring further the pathophysiology of GATA2-related deficiencies in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping