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

Research output: Contribution to journalArticle

Authors

  • Tomasz Dobrzycki
  • Monika Krecsmarik
  • Cansu Koyunlar
  • Rossella Rispoli
  • Joke Peulen-Zink
  • Kirsten Gussinklo
  • Bakhta Fedlaoui
  • Emma de Pater
  • Roger Patient

Colleges, School and Institutes

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 gata2a Δi4/Δi4 larvae showed normal numbers of HSPCs, a recovery mediated by Notch signalling driving gata2b and runx1 expression in HE. However, gata2a Δi4/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.

Details

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