Synergism of interferon-gamma and stem cell factor on the development of murine hematopoietic progenitors in serum-free culture

Shiohara, Mayumi; Koike, K; Nakahata, T

doi:10.1182/blood.v81.6.1435.bloodjournal8161435

Cited by 3 publications

(4 citation statements)

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“…c‐ jun is required for progression through G 1 and for trans‐activation of the cyclin D1 gene in fibroblasts (Wisdom et al ., 1999), thus helping to provide a link between the response to growth factors and cell cycle regulation. Deregulated expression of c‐ myc and c‐ jun is likely to be important in the abnormal proliferation of Stat1‐null cells in response to IFN‐γ, which can serve as a growth factor for some cells (Caux et al ., 1992; Shiohara et al ., 1993). IFN‐γ suppressed the expression of c‐ myc in wild‐type cells and is likely to be important in regulating the switch between growth arrest and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the inhibition by IFN‐γ of the growth of the colon carcinoma cell line HCT116 is independent of p21 (Sharma and Iozzo, 1998). IFN‐γ can stimulate rather than suppress the growth of certain cells (Caux et al ., 1992; Shiohara et al ., 1993), but the basis of this paradoxical activity is unclear. Stat1, and indeed other Stats, can also mediate negative regulation of gene expression in response to effectors other than the IFNs.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways

Ramana

Grammatikakis

Chernov

et al. 2000

EMBO J

286

233

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Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c-myc expression. IFN-gamma suppresses c-myc in wild-type mouse embryo fibroblasts, but not in Stat1-null cells, where IFNs induce c-myc mRNA rapidly and transiently, thus revealing a novel signaling pathway. Both tyrosine and serine phosphorylation of Stat1 are required for suppression. Induced expression of c-myc is likely to contribute to the proliferation of Stat1-null cells in response to IFNs. IFNs also suppress platelet-derived growth factor (PDGF)-induced c-myc expression in wild-type but not in Stat1-null cells. A gamma-activated sequence element in the promoter is necessary but not sufficient to suppress c-myc expression in wild-type cells. In PKR-null cells, the phosphorylation of Stat1 on Ser727 and transactivation are both defective, and c-myc mRNA is induced, not suppressed, in response to IFN-gamma. A role for Raf-1 in the Stat1-independent pathway is revealed by studies with geldanamycin, an HSP90-specific inhibitor, and by expression of a mutant of p50(cdc37) that is unable to recruit HSP90 to the Raf-1 complex. Both agents abrogated the IFN-gamma-dependent induction of c-myc expression in Stat1-null cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways

Ramana

Grammatikakis

Chernov

et al. 2000

EMBO J

286

233

View full text Add to dashboard Cite

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“…The Mef TF facilitates the quiescent HSCs transition from G 0 to G 1 phase ( Huck et al, 2014 ). Other TFs that maintain the stemness of HSCs are SON, Tal1 or SCL, RUNX1, LMO2, GATA-2, HOXA9, and HOXA1, as summarized in Table 1 ( Blume-Jensen et al, 1991 ; Shiohara et al, 1993 ; Rossi et al, 2007 ; Park et al, 2013 ; Wang and Ema, 2016 ; Bhatlekar et al, 2018 ).…”

Section: Factors For Hematopoietic Stem Cells Stemness and Self-renewalmentioning

confidence: 99%

“…c-Kit maintains a balance between self-renewal and differentiation among HSCs via the c-Kit/SCF axis ( Mirantes et al, 2014 ; Birbrair and Frenette, 2016 ). The c-Kit lo population stays higher in the hierarchy than c-Kit hi , and the transition from c-Kit lo to c-Kit hi is mediated by c-Cbl ( Shiohara et al, 1993 ; Huck et al, 2014 ). It is observed that c-Kit lo HSCs exhibit long-term reconstitution with enhanced self-renewal as compared to c-Kit hi .…”

Section: Factors For Hematopoietic Stem Cells Stemness and Self-renewalmentioning

confidence: 99%

Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects

Mann¹,

Sengar

Verma

et al. 2022

Front. Cell Dev. Biol.

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Hematopoietic stem cells (HSCs) possess two important properties such as self-renewal and differentiation. These properties of HSCs are maintained through hematopoiesis. This process gives rise to two subpopulations, long-term and short-term HSCs, which have become a popular convention for treating various hematological disorders. The clinical application of HSCs is bone marrow transplant in patients with aplastic anemia, congenital neutropenia, sickle cell anemia, thalassemia, or replacement of damaged bone marrow in case of chemotherapy. The self-renewal attribute of HSCs ensures long-term hematopoiesis post-transplantation. However, HSCs need to be infused in large numbers to reach their target site and meet the demands since they lose their self-renewal capacity after a few passages. Therefore, a more in-depth understanding of ex vivo HSCs expansion needs to be developed to delineate ways to enhance the self-renewability of isolated HSCs. The multifaceted self-renewal process is regulated by factors, including transcription factors, miRNAs, and the bone marrow niche. A developed classical hierarchical model that outlines the hematopoiesis in a lineage-specific manner through in vivo fate mapping, barcoding, and determination of self-renewal regulatory factors are still to be explored in more detail. Thus, an in-depth study of the self-renewal property of HSCs is essentially required to be utilized for ex vivo expansion. This review primarily focuses on the Hematopoietic stem cell self-renewal pathway and evaluates the regulatory molecular factors involved in considering a targeted clinical approach in numerous malignancies and outlining gaps in the current knowledge.

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Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin

Choi

Muta

Wickrema

et al. 2000

Blood

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Based on the hypothesis that interferon gamma (IFN-γ) may have stimulating effects on survival of hematopoietic progenitor cells, we examined the effect of IFN-γ on apoptosis of mature erythroid colony-forming cells (ECFCs) derived from human peripheral blood obtained from normal, healthy volunteers. When the cells were cultured in the presence of IFN-γ, even without erythropoietin (EPO), the viability of the cells was maintained for at least 36 hours. When apoptosis of ECFCs was assessed by flow cytometric analysis', using annexin V, IFN-γ reduced the extent of apoptosis of the cells, as well as EPO. DNA fragmentation of ECFCs was also reduced by IFN-γ. In cells cultured with IFN-γ alone, expression of Bcl-x was detected but the level of expression decreased gradually during incubation for 36 hours, and the expression level was lower than incubation with EPO. Fas expression and activation of downstream caspases were assessed by flow cytometric analysis or fluorometric protease assay. IFN-γ induced Fas expression of the cells without the activation of caspase8 or caspase3 during 16 hours of incubation, while deprivation of EPO induced expression of Fas and the activation of both caspase8 and caspase3. We propose that IFN-γ produces a stimulating signal for the survival of mature erythroid progenitor cells by reducing apoptosis through a mechanism other than modulating Fas and one related to the expression of Bcl-x.

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Synergism of interferon-gamma and stem cell factor on the development of murine hematopoietic progenitors in serum-free culture

Cited by 3 publications

References 0 publications

Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways

Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways

Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects

Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin

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