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Review
. 2020 Jan 16;2(1):1-6.
doi: 10.1097/BS9.0000000000000040. eCollection 2020 Jan.

Dynamic regulation of GATA2 in fate determination in hematopoiesis: possible approach to hPSC-derived hematopoietic stem/progenitor cells

Ya Zhou  1 , Bin Mao  1 , Yijin Chen  1 , Yuan Xue  1 , Bo Chen  1 , Yonggang Zhang  1 , Feng Ma  1   2
Affiliations
Review

Dynamic regulation of GATA2 in fate determination in hematopoiesis: possible approach to hPSC-derived hematopoietic stem/progenitor cells

Ya Zhou et al. Blood Sci. .

Abstract

GATA2, a principal member of the GATA family, plays important roles in the generation and maintenance of hematopoietic stem/progenitor cells. Among the three mRNA transcripts, the distal first exon of GATA2 (IS exon) is specific for hematopoietic and neuronal cells. GATA2 mutants with abnormal expression are often present in acute myeloid leukemia-related familial diseases and myelodysplastic syndrome, indicating the crucial significance of GATA2 in the proper maintenance of blood system functions. This article offers an overview of the regulation dynamics and function of GATA2 in the generation, proliferation, and function of hematopoietic stem cells in both mouse and human models. We acknowledge the current progress in the cell fate determination mechanism by dynamic GATA2 expression. The gene modification approaches for inspecting the role of GATA2 in definitive hematopoiesis demonstrate the potential for acquiring hPSC-derived hematopoietic stem cells via manipulated GATA2 regulation.

Keywords: GATA2; Hematopoiesis; Stem cells.

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Conflict of interest statement

Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

Figures

Figure 1
Figure 1
Genomic and protein structure and cis-regulatory elements of GATA2. (A) Schematic representation of human GATA2. The three isoforms IS, IG, and unnamed of human GATA-2 have 6, 6 and 7 exons, respectively. (B) Schematic representation of human GATA2 protein. The encoded protein possesses two transactivation domains(TAD), a negative regulatory domain (NRD), two zinc finger (ZnF) domains, and a nuclear localization signal (NLS). (C) Cis-regulatory elements of GATA2. The −77-kb region, promoter-neighboring region (−3.9, −2.8, and −1.8 kb), and +9.5-kb region are depicted in red. Human and mouse hematopoietic disorders caused by mutations in the cis-regulatory elements and coding region of GATA2 have been indicated.
Figure 2
Figure 2
Schematic illustration of the role of abnormal GATA2 expression in mice and humans. (A) Schematic representation of the role of Gata2 knockout in the EHT in the E10.5 mouse AGM region. (B) Model of Gata2 expression dynamics and pulsatile characteristic during EHT in the mouse AGM region at embryonic day (E) 10.5. EHT is accompanied by the transition from HE, and bulging cells emerge from the wall of AGM to intra-aortic hematopoietic cluster cells (IAHCs), which are round cells found in clusters adjacent to the endothelial layer. EHT cell types (top) are shown with accompanying dynamic Gata2 expression changes in EHT directly below. MFI (bright green) and pulse parameters (dark green sinusoids) are shown for Gata2V/+ (middle) and Gata2V/− (bottom) EHT subset cells. MFI: mean fluorescent intensity. (C) Schematic illustration of the role of GATA2 overexpression and haploinsufficiency in mouse bone marrow cells. (D and E) Schematic illustration of the role of inducible GATA2 overexpression in human cord blood cells and hESCs.
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