Inhibition of Caspase-mediated Anoikis Is Critical for Basic Fibroblast Growth Factor-sustained Culture of Human Pluripotent Stem Cells

Wang, Xiaofang; Lin, Ge; Martins-Taylor, Kristen; Zeng, Hui; Xu, Ren‐He

doi:10.1074/jbc.m109.052290

Cited by 65 publications

(65 citation statements)

References 42 publications

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“…It was reported that inhibition of caspasemediated anoikis by bFGF is dependent on activation of ERK and AKT in human ES cells. 39 We also showed that the inhibition of ERK or AKT irrespective of the presence of the imatinib resulted in the decrease of the attached cell numbers. Some key molecules essential for the maintenance of iPSCs may compensate for the BCR-ABL inhibition in the CML-iPSCs through downstream ERK and AKT signaling pathways.…”

Section: Generation Of Cml-derived Ipscsmentioning

confidence: 77%

“…38 The phosphorylation status of ERK1/2, AKT, JNK, and STAT5 in CML-iPSCs, which are essential for the survival of BCR-ABL (ϩ) hematopoietic progenitors, were evaluated after imatinib treatment. The phosphorylation of ERK1/2, AKT, and JNK, which are also essential for the maintenance of iPSCs and ES cells, 39,40 were unchanged after treatment in the CML-iPSCs although they were decreased in the CML-iPSCs-derived hematopoietic cells ( Figure 6B). The phosphorylation of CRKL and STAT5, which were not activated in the normal iPSCs, was decreased in both CMLiPSCs and CML-iPSCs-derived hematopoietic cells ( Figure 6B).…”

Section: Bcr-abl Dependence Is Lost In the Cml-ipscsmentioning

confidence: 99%

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Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples

Kumano

Arai

Hosoi

et al. 2012

Blood

145

138

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Induced pluripotent stem cells (iPSCs)can be generated by the expression of defined transcription factors not only from normal tissue, but also from malignant cells. Cancer-derived iPSCs are expected to provide a novel experimental opportunity to establish the disease model. We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. Remarkably, the CML-iPSCs were resistant to imatinib although they consistently

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Section: Generation Of Cml-derived Ipscsmentioning

confidence: 77%

Section: Bcr-abl Dependence Is Lost In the Cml-ipscsmentioning

confidence: 99%

Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples

Kumano

Arai

Hosoi

et al. 2012

Blood

145

138

View full text Add to dashboard Cite

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“…However, this extreme model has been challenged in subsequent publications. Wang et al reported that exogenous IGF2 alone was insufficient to maintain undifferentiated growth in defined (TeSR1) culture conditions (Wang et al, 2009) and suggested that FGF has a direct role in blocking caspase-activated apoptosis through anoikis in ES cells. An anti-apoptotic action of FGF is also supported by data from Eiselleova et al, who were able to detect all four FGF receptors and weak FGF2 binding to undifferentiated hES colonies (Eiselleova et al, 2009).…”

Section: Human Es Cells: the Enigmatic Role Of Fgf Signalingmentioning

confidence: 99%

The role of FGF/Erk signaling in pluripotent cells

2010

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SummaryFibroblast growth factor (FGF) signaling controls fundamental processes such as proliferation, differentiation and migration throughout mammalian development. Here we discuss recent discoveries that implicate FGF/Erk signaling in the control of pluripotency and lineage specification in several different stem cell states, including the separation of pluripotent epiblast and primitive endoderm in the blastocyst, the lineage priming of embryonic stem (ES) cells, and in the stabilization of the metastable state of mouse epiblast and human ES cells. Understanding how extrinsic signals such as FGF regulate different stem cell states will be crucial to harvest the clinical promise of induced pluripotent and embryo-derived stem cells. Key words: FGF signaling, Stem cells, Embryonic development IntroductionFibroblast growth factors (FGFs) and their receptor tyrosine kinases control a multitude of developmental processes, including proliferation, survival, migration and differentiation. In this review, we discuss recently emerging evidence that FGF signaling plays an important role in regulating pluripotency and lineage segregation in both the early mouse embryo and in pluripotent mammalian stem cells. Although mouse and human embryonic stem (ES) cells are both derived from the pluripotent inner cell mass (ICM) cells of the pre-implantation blastocyst, they exhibit fundamental differences, whereby mouse ES cells appear to represent a developmentally more 'naïve' pre-implantation state and human ES cells a 'primed' post-implantation state ), similar to mouse epiblast-derived stem cells (EpiSCs) (Brons et al., 2007;Tesar et al., 2007). Intriguing recent findings suggest an important role for FGF/extracellular signal-regulated kinase (Erk) signaling in promoting the transition from a naïve to a primed state and in preventing primed cells from reverting back to a naïve state, in effect stabilizing the primed cell state (Hanna et al., 2009;Li et al., 2009;Greber et al., 2010;Hanna et al., 2010). Modulating FGF/Erk signaling might therefore facilitate the conversion of conventional human ES cells into a more naïve and mouse-like state. The existence of multiple and possibly interconvertible pluripotent stem cell states controlled by the extrinsic signaling environment could have significant implications not only for early developmental biology, but also for the field of reprogramming and induced pluripotency.FGF signaling FGF signaling is activated by a ligand-receptor interaction that results in the autophosphorylation of tyrosine residues in the intracellular region of an FGF receptor (FGFR). The signal is further relayed through four distinct pathways: the Janus kinase/signal transducer and activator of transcription (Jak/Stat), phosphoinositide phospholipase C (PLCg), phosphatidylinositol 3-kinase (PI3K) and Erk pathways (Dailey et al., 2005) (Fig. 1). The formation of a complex between FGFR, fibroblast growth factor receptor substrate 2 (Frs2a), Src homology region 2 domaincontaining phosphatase 2 (Shp2; also known ...

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“…1D). In some cases, LIF (Magni et al, 2007) and bFGF (Wang et al, 2009) transmit signals through the AKT pathway, and it is likely that forced activation of AKT might have strengthened LIF and bFGF signals (Fig. 7).…”

Section: Relationship Between the Akt Pathway And Lif Or Bfgf Signalingmentioning

confidence: 99%

The majority of early primordial germ cells acquire pluripotency by AKT activation

et al. 2014

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Primordial germ cells (PGCs) are undifferentiated germ cells in embryos, the fate of which is to become gametes; however, mouse PGCs can easily be reprogrammed into pluripotent embryonic germ cells (EGCs) in culture in the presence of particular extracellular factors, such as combinations of Steel factor (KITL), LIF and bFGF (FGF2). Early PGCs form EGCs more readily than do later PGCs, and PGCs lose the ability to form EGCs by embryonic day (E) 15.5. Here, we examined the effects of activation of the serine/threonine kinase AKT in PGCs during EGC formation; notably, AKT activation, in combination with LIF and bFGF, enhanced EGC formation and caused ∼60% of E10.5 PGCs to become EGCs. The results indicate that the majority of PGCs at E10.5 could acquire pluripotency with an activated AKT signaling pathway. Importantly, AKT activation did not fully substitute for bFGF and LIF, and AKT activation without both LIF and bFGF did not result in EGC formation. These findings indicate that AKT signal enhances and/or collaborates with signaling pathways of bFGF and of LIF in PGCs for the acquisition of pluripotency.

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Inhibition of Caspase-mediated Anoikis Is Critical for Basic Fibroblast Growth Factor-sustained Culture of Human Pluripotent Stem Cells

Cited by 65 publications

References 42 publications

Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples

Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples

The role of FGF/Erk signaling in pluripotent cells

The majority of early primordial germ cells acquire pluripotency by AKT activation

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