Regulation of Stem Cell Pluripotency and Neural Differentiation by Lysophospholipids

Pitson, Stuart M.; Pébay, Alice

doi:10.1159/000231891

Cited by 57 publications

(46 citation statements)

References 130 publications

(204 reference statements)

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“…Our results show that both undifferentiated hPSCs and neural differentiated hPSCs express LPA [1][2][3][4][5] mRNA, confi rming our previous RT-PCR data ( 8,39,54 ), and they show that LPA 2 and LPA 4 are the most abundant mRNA in undifferentiated hPSCs and neurospheres. Modulation in the receptor expression profi le was observed following neural differentiation with an upregulation of LPA 1 mRNA during the early neural commitment of hPSCs (noggin-treated stage), followed by its downregulation during later differentiation (neurosphere stage).…”

Section: Lpa Induces Rhoa Activationsupporting

confidence: 92%

“…Further, LPA has been shown to be a survival factor, a pro-apoptotic agent or a prodifferentiation factor of NS/PCs (16)(17)(18). Comparably, LPA has also been described as a proliferative, survival, or prodifferentiation factor in some neuroblasts but not all ( 8 ). It was recently shown that LPA can induce fetal hydrocephalus in the mouse by an aberrant activation of Lpa 1 on NS/PCs during development ( 19 ).…”

mentioning

confidence: 99%

“…LPA's effects on NS/PCs and neuroblasts seem to vary depending on the origin of the cells ( 8 ). These differences might be the consequence of discrepancies in terms of cell source (different lines and differentiation stages), appropriate conjugated secondary antibodies (Alexa Fluor 555 or 488, Cy3, Molecular Probes-Invitrogen).…”

mentioning

confidence: 99%

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Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

Frisca

Crombie

Dottori

et al. 2013

Journal of Lipid Research

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Section: Lpa Induces Rhoa Activationsupporting

confidence: 92%

mentioning

confidence: 99%

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Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

Frisca

Crombie

Dottori

et al. 2013

Journal of Lipid Research

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“…Indeed, S1P has been shown to maintain self-renewal of human embryonic stem cells in cooperation with platelet-derived growth factor 36 . Humaninduced pluripotent stem cells have also been shown to express S1PR3 messenger RNAs, although their biological effects in induced pluripotent stem cells are yet to be elucidated 37 . We postulate that S1P might have self-renewal properties, and play a key role in stem cell regulation.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

et al. 2014

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Many tumours originate from cancer stem cells (CSCs), which is a small population of cells that display stem cell properties. However, the molecular mechanisms that regulate CSC frequency remain poorly understood. Here, using microarray screening in aldehyde dehydrogenase (ALDH)-positive CSC model, we identify a fundamental role for a lipid mediator sphingosine-1-phosphate (S1P) in CSC expansion. Stimulation with S1P enhances ALDH-positive CSCs via S1P receptor 3 (S1PR3) and subsequent Notch activation. CSCs overexpressing sphingosine kinase 1 (SphK1), an S1P-producing enzyme, show increased ability to develop tumours in nude mice, compared with parent cells or CSCs. Tumorigenicity of CSCs overexpressing SphK1 is inhibited by S1PR3 knockdown or S1PR3 antagonist. Breast cancer patient-derived mammospheres contain SphK1 þ /ALDH1 þ cells or S1PR3 þ /ALDH1 þ cells. Our findings provide new insights into the lipid-mediated regulation of CSCs via Notch signalling, and rationale for targeting S1PR3 in cancer.

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“…LPA and S1P were shown to modulate proliferation, survival, differentiation, and migration of embryonic and neural stem cells [20]. In mouse hematopoietic progenitors, LPA 1 , LPA 2 , and S1P 1-4 , but not LPA 3 or S1P 5 , were expressed in primitive Lin-Sca þ Kit þ cells isolated from bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

et al. 2011

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Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through activating G protein-coupled receptors. LPA receptor 3 (LPA 3 ) is a member of the endothelial differentiation gene family, which regulates differentiation and development of the circulation system. However, the relationship among the LPA receptors (LPARs) and erythropoiesis is still not clear. In this study, we found that erythroblasts expressed both LPA 1 and LPA 3 , and erythropoietic defects were observed in zLPA 3 antisense morpholino oligonucleotide-injected zebrafish embryos. In human model, our results showed that LPA enhanced the erythropoiesis in the cord blood-derived human hematopoietic stem cells (hHSCs) with erythropoietin (EPO) addition in the plasma-free culture. When hHSCs were treated with Ki16425, an antagonist of LPA 1 and LPA 3 , erythropoietic process of hHSCs was also blocked, as detected by mRNA and protein expressions of CD71 and GlyA. In the knockdown study, we further demonstrated that specific knockdown of LPA 3 , not LPA 1 , blocked the erythropoiesis. The translocation of b-catenin into the nucleus, a downstream response of LPAR activation, was blocked by Ki16425 treatment. In addition, upregulation of erythropoiesis by LPA was also blocked by quercetin, an inhibitor of the b-catenin/ T-cell factor pathway. Furthermore, the enhancement of LPA on erythropoiesis was diminished by blocking c-Junactivated kinase/signal transducer and activator of transcription and phosphatidylinositol 3-kinase/AKT activation, the downstream signaling pathways of EPO receptor, suggested that LPA might play a synergistic role with EPO to regulate erythropoietic process. In conclusion, we first reported that LPA participates in EPO-dependent erythropoiesis through activating LPA 3 .

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Regulation of Stem Cell Pluripotency and Neural Differentiation by Lysophospholipids

Cited by 57 publications

References 130 publications

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

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