AI Article Synopsis

  • - Gata2 is essential for creating Haematopoietic Stem and Progenitor Cells (HSPCs) from haemogenic endothelium, and issues with Gata2 can cause blood disorders.
  • - Researchers deleted a critical enhancer in zebrafish that affects gata2a expression and found that while gata2a larvae initially had normal HSPC numbers, adult gata2a fish displayed problems like edema and bone marrow failure.
  • - The study highlights the importance of Gata2a regulated by the enhancer for proper embryonic development and ongoing stem cell function in adults, with potential implications for understanding GATA2-related diseases.

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

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018942PMC
http://dx.doi.org/10.1038/s42003-020-0798-3DOI Listing

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