A Fluorescent Rosamine Compound Selectively Stains Pluripotent Stem Cells

Im, Chang Nim; Kang, Nae Gyu; Ha, Hyung Ho; Bi, Xuezhi; Lee, Jae Jung; Park, Sung-Jin; Lee, Sang Yeon; Vendrell, Marc; Kim, Yun Kyung; Lee, Jung Hoon; Li, Jun; Ahn, Young Hoon; Feng, Bo; Ng, Huck Hui; Yun, Seong Wook; Chang, Young Tae

doi:10.1002/anie.201002463

Cited by 72 publications

(32 citation statements)

References 11 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, Garros-Regulez et al found that TMZ resistance was positively correlated with SOX2 expression in glioblastoma cells and in cells expressing high levels of SOX2 [24]. When we tested this in our culture system, we also consistently observed that SPs expressing SOX2 [15,25] were more resistant to TMZ treatment compared with ML cells, suggesting that our culture system is suitable for in vitro study of GSCs and the drug response [26]. Based on this, we examined the effect of BIS or HSF1 depletion in combination with TMZ treatment, and found that apoptosis was increased (as measured by PARP cleavage), SOX2 levels were decreased, and SP formation was increased.…”

Section: Discussionmentioning

confidence: 52%

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

Yun

Lee

2017

IJMS

Self Cite

View full text Add to dashboard Cite

Heat shock factor 1 (HSF1), a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (B-cell lymphoma 2) interacting cell death suppressor (BIS). HSF1 also directly interacts with BIS, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs). In this study, we examined whether small interfering RNA-mediated BIS knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP)-forming conditions. Consistent with BIS depletion, HSF1 knockdown also reduced sex determining region Y (SRY)-box 2 (SOX2) expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2) activity. When HSF1 or BIS knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting BIS or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.

show abstract

Section: Discussionmentioning

confidence: 52%

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

Yun

Lee

2017

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies demonstrated that glioblastoma exhibits remarkable heterogeneity, including a small population of self-renewing glioblastoma stem cells (GSCs) [2, 3]. In addition to self-renewal activity, GSCs share similar properties of normal stem cells, such as multilineage differentiation to astrocytes, oligodendrocytes, or neurons, as well as expression of a variety of stemness-related genes, including SOX-2 and NESTIN [4–6]. GSCs also exhibit cancer stem-cell-like features, such as invasion, modulation of immune response, and high motility, which likely contribute to the highly infiltrative nature of glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes

Yun

Song

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

Glioblastoma stem cells (GSCs) are a subpopulation of highly tumorigenic and stem-like cells that are responsible for resistance to conventional therapy. Bcl-2-intreacting cell death suppressor (BIS; also known as BAG3) is an anti-apoptotic protein that is highly expressed in human cancers with various origins, including glioblastoma. In the present study, to investigate the role of BIS in GSC subpopulation, we examined the expression profile of BIS in A172 and U87-MG glioblastoma cell lines under specific in vitro culture conditions that enrich GSC-like cells in spheres. Both BIS mRNA and protein levels significantly increased under the sphere-forming condition as compared with standard culture conditions. BIS depletion resulted in notable decreases in sphere-forming activity and was accompanied with decreases in SOX-2 expression. The expression of STAT3, a master regulator of stemness, also decreased following BIS depletion concomitant with decreases in the nuclear levels of active phosphorylated STAT3, while ectopic STAT3 overexpression resulted in recovery of sphere-forming activity in BIS-knockdown glioblastoma cells. Additionally, immunoprecipitation and confocal microscopy revealed that BIS physically interacts with STAT3. Furthermore, BIS depletion increased STAT3 ubiquitination, suggesting that BIS is necessary for STAT3 stabilization in GSC-like cells. BIS depletion also affected epithelial-to-mesenchymal transition-related genes as evidenced by decrease in SNAIL and MMP-2 expression and increase in E-cadherin expression in GSC-like cells. Our findings suggest that high levels of BIS expression might confer stem-cell-like properties on cancer cells through STAT3 stabilization, indicating that BIS is a potential target in cancer therapy.

show abstract

“…Rapid efflux of ABCG2 substrates in emerging iPSC cell colonies result in Hoechst dim phenotype that, in combination with expression of other markers, is reported to be an accurate predictor of reprogramming success (11). A recent study screened a large chemical library and identified CDy1, a rosamine analog that specifically stains pluripotent stem cells 16. The mode of staining by this dye remains largely unknown, nevertheless, it stains both live human ESC and iPSC and can be used in fluorescence-activated cell sorting 17…”

Section: Discussionmentioning

confidence: 99%

Novel Live Alkaline Phosphatase Substrate for Identification of Pluripotent Stem Cells

Singh¹,

Quintanilla

Grecian³

et al. 2012

Stem Cell Rev and Rep

View full text Add to dashboard Cite

A Fluorescent Rosamine Compound Selectively Stains Pluripotent Stem Cells

Cited by 72 publications

References 11 publications

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes

Novel Live Alkaline Phosphatase Substrate for Identification of Pluripotent Stem Cells

Contact Info

Product

Resources

About