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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
192 Downloads (Pure)

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.

Original languageEnglish
Article number71
Number of pages14
JournalCommunications Biology
Volume3
Issue number1
DOIs
Publication statusPublished - 13 Feb 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Medicine (miscellaneous)

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