Glia maturation factor gamma, is a novel diagnostic marker of leukemia, has TAL1 binding sites in its promoter

Zia, Saadiya; Baqri, Nudrat; Shahid, Ramla

doi:10.1016/j.jksus.2018.07.015

Cited by 3 publications

(3 citation statements)

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“…During tumor progression, tumor cells undergo invasion and metastasis through EMT [ 63 ]. Interestingly, gmfg promoted EMT of tumor cells [ 64 ], and it was revealed to be highly associated with tumor prognosis including leukemia [ 23 , 64 – 66 ]. Moreover, externally applied shear stress is able to induce an EMT-like process termed endothelial-to-mesenchymal transition (EndMT) at a low value compatible to the magnitude experienced by the developing embryo during EHT [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is reasonable to consider whether the findings reported in our study may also apply in other types of tumor stem cells. Given that in certain studies gmfg was considered as a potential predictive factor in the development of cancer [ 23 , 68 ], the impact of biomechanical microenvironment should be taken into account in the treatment of diseases related to gmfg .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, genetic inhibition of gmfg attenuated the migration and/or chemotaxis of monocytes, neutrophils, T cells and B cells [ 18 – 22 ]. Another study reported that gmfg expression was significantly elevated in leukemia patients [ 23 ]. Nevertheless, whether and how gmfg regulates aspects of embryonic HSPCs have not been systematically explored.…”

Section: Introductionmentioning

confidence: 99%

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Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells

Luo

Cai

et al. 2023

Stem Cell Res Ther

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Background In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development. Methods In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development. Loss and gain-of-function strategies were applied to study the biological function of gmfg. Whole-mount in situ hybridization, confocal microscopy, flow cytometry, and western blotting were used to evaluate changes in the number of various hematopoietic cells and expression levels of cell proliferation, cell apoptosis and hematopoietic-related markers. RNA-seq was performed to screen signaling pathways responsible for gmfg deficiency-induced defects in HSPC initiation. The effect of gmfg on YAP sublocalization was assessed in vitro by utilizing HUVEC cell line. Results We took advantage of zebrafish embryos to illustrate that loss of gmfg impaired HSPC initiation and maintenance. In gmfg-deficient embryos, the number of hemogenic endothelium and HSPCs was significantly reduced, with the accompanying decreased number of erythrocytes, myelocytes and lymphocytes. We found that blood flow modulates gmfg expression and gmfg overexpression could partially rescue the reduction of HSPCs in the absence of blood flow. Assays in zebrafish and HUVEC showed that gmfg deficiency suppressed the activity of YAP, a well-established blood flow mediator, by preventing its shuttling from cytoplasm to nucleus. During HSPC initiation, loss of gmfg resulted in Notch inactivation and the induction of Notch intracellular domain could partially restore the HSPC loss in gmfg-deficient embryos. Conclusions We conclude that gmfg mediates blood flow-induced HSPC maintenance via regulation of YAP, and contributes to HSPC initiation through the modulation of Notch signaling. Our findings reveal a brand-new aspect of gmfg function and highlight a novel mechanism for embryonic HSPC development.

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