Multifaceted Actions of GFI1 and GFI1B in Hematopoietic Stem Cell Self-Renewal and Lineage Commitment

Abstract

needed to convert adult endothelial cells or fibroblasts into HSCs. This role of GFI1 and GFI1B bears high significance for the ongoing effort to generate hematopoietic stem and progenitor cells de novo for the autologous treatment of blood disorders such as leukemia and lymphoma.

Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus

“…Further, the role of GFI1 on IE transcription and viral replication could depend on the type of HCMV infection (acutely infected cells versus “chronically-infected” CTH cells), the cell type involved (fibroblasts versus epithelial-derived CTH cells) and the differentiation state and lineage commitment of the infected cells. 68 Altogether, the enhanced viral replication observed in CTH cells treated with EZH2 inhibitors could be mostly explained by the enhanced presence of GFI1 on the MIEP parallel to the enhanced H3K4Me3 rather than the decreased H3K27Me3 chromatin marks (Suppl. Figure 7).…”

“…Finally, GFI1 may have additional non-transcriptional functions and interacts with a number of proteins involved in DNA repair. 68 An E2F1-mediated DNA damage response contributes to the replication of HCMV 69 making the role of GFI1 even more complex in HCMV replication. The role of GFI1 on HCMV replication definitively needs further studies.…”

Tet-mediated DNA demethylation regulates specification of hematopoietic stem and progenitor cells during mammalian embryogenesis

“…Specification of ECs to HECs and subsequently to HSPCs is guided by timely expression of hematopoiesis-specific genes including members of the Runx, Gata, and Gfi1 families of master transcription factors. Proper activation of these genes in ECs and HECs and their expression in HSPCs is essential for normal embryonic hematopoiesis (30)(31)(32)(33).…”

Discovery of target genes and pathways of blood trait loci using pooled CRISPR screens and single cell RNA sequencing

“…5E-F, Table S4D). Together with Cluster A's high enrichment of GFI1B binding sites and increased expression upon inhibiting GFI1B (a repressor), this suggests that these genes are the primary targets of GFI1B to suppress differentiation in non-erythrocytic and non-megakaryocytic pathways (36). Cluster B genes were highly expressed in granulocyte-monocyte progenitors (GMP) and their differentiated cell types, including monocytes and dendritic cells (Fig.…”

“…GFI1B encodes a transcription factor central to hematopoiesis (33)(34)(35)(36), therefore we examined GFI1B ChIP-seq data in K562 cells (35) near the transcription start sites of rs524137-GFI1B transregulated genes and observed GFI1B binding (Fig. 4E, Table S4A), with a significant enrichment across all rs524137-GFI1B trans-regulated genes (Fig.…”