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  • Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis.

Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis.

Communications biology (2020-02-15)
Tomasz Dobrzycki, Christopher B Mahony, Monika Krecsmarik, Cansu Koyunlar, Rossella Rispoli, Joke Peulen-Zink, Kirsten Gussinklo, Bakhta Fedlaoui, Emma de Pater, Roger Patient, Rui Monteiro
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.

MATERIALS
Product Number
Brand
Product Description

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DPX Mountant for histology, slide mounting medium
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Giemsa Stain, Modified Solution, (for the staining (of cellular blood components and blood parasites))
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p-Xylene-bis(N-pyridinium bromide), ≥95% (TLC)
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May-Grünwald Stain