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

Frisca, Frisca; Crombie, Duncan E.; Dottori, Mirella; Goldshmit, Yona; Pébay, Alice

doi:10.1194/jlr.m032284

Cited by 38 publications

(26 citation statements)

References 78 publications

(148 reference statements)

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“…Two members of the ROCK family (ROCK1 and ROCK2), as the direct downstream effectors of RhoA, have been shown to be important regulators of proliferation, differentiation and senescence. In human neural stem/ progenitor cells, lysophosphatidic acid (LPA) inhibited the neuronal differentiation through activating ROCK [34]. In human embryonic stem cells, the ROCK inhibitor promoted cellular proliferation and Fig.…”

Section: Discussionmentioning

confidence: 99%

miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1

Chen

Wang

Liu

et al. 2015

Bone

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Section: Discussionmentioning

confidence: 99%

miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1

Chen

Wang

Liu

et al. 2015

Bone

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“…Likewise, noggin induces the progressive neural patterning of iPSCs after which the propagation of iPSC-derived colonies in a suspension medium containing neural basal medium (NBM) supplemented with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) induces their aggregation and formation of spherical-like clusters termed neurospheres. At the neurosphere stage, the efficient generation and expansion of NSCs/NPCs is taking place ( Frisca et al, 2013 ), consisting of a heterogeneous population of NSCs ( Valenzuela et al, 2007 ) with a reduced risk of tumor formation after transplantation ( Yuan et al, 2013 ;Zhang et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres

Tafreshi

Sylvain

Sun

et al. 2015

Biological Chemistry

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Induced pluripotent stem cell (iPSC)-derived neurospheres, which consist mainly of neural progenitors, are considered to be a good source of neural cells for transplantation in regenerative medicine. In this study, we have used lithium chloride, which is known to be a neuroprotective agent, in an iPSC-derived neurosphere model, and examined both the formation rate and size of the neurospheres as well as the proliferative and apoptotic status of their contents. Our results showed that lithium enhanced the formation and the sizes of the iPSC-derived neurospheres, increased the number of Ki67-positive proliferating cells, but reduced the number of the TUNEL-positive apoptotic cells. This increased number of Ki67 proliferating cells was secondary to the decreased apoptosis and not to the stimulation of cell cycle entry, as the expression of the proliferation marker cyclin D1 mRNA did not change after lithium treatment. Altogether, we suggest that lithium enhances the survival of neural progenitors and thus the quality of the iPSC-derived neurospheres, which may strengthen the prospect of using lithium-treated pluripotent cells and their derivatives in a clinical setting.

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“…A growing number of reports clearly demonstrate that lipid metabolisms determine the fate of stem cells . Among lipid metabolites, lysophosphatidic acid (LPA), a potent lysophospholipid, has attracted a great amount of attention because it is a critical regulator of proliferation, migration, and differentiation of adult stem cells as well as embryonic stem cells . Autotaxin (ATX) is a mitogenic‐like phosphodiesterase originally identified as an “autocrine motility factor,” which was shown to have lysophospholipase D (lysoPLD) activity, converting lysophosphatidylcholine to LPA .…”

Section: Introductionmentioning

confidence: 99%

Autotaxin-LPA Axis Regulates hMSC Migration by Adherent Junction Disruption and Cytoskeletal Rearrangement Via LPAR1/3-Dependent PKC/GSK3β/β-Catenin and PKC/Rho GTPase Pathways

Ryu

Han

2015

Stem Cells

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Bioactive molecules and stem cell-based regenerative engineering is emerging a promising approach for regenerating tissues. Autotaxin (ATX) is a key enzyme that regulates lysophosphatidic acid (LPA) levels in biological fluids, which exerts a wide range of cellular functions. However, the biological role of ATX in human umbilical cord blood-derived mesenchymal stem cells (hMSCs) migration remains to be fully elucidated. In this study, we observed that hMSCs, which were stimulated with LPA, accelerated wound healing, and LPA increased the migration of hMSCs into a wound site in a mouse skin wound healing model. In an experiment to investigate the effect of LPA on hMSC migration, ATX and LPA increased hMSC migration in a dosedependent manner, and LPA receptor 1/3 siRNA transfections inhibited the ATX-induced cell migration. Furthermore, LPA increased Ca 21 influx and PKC phosphorylation, which were blocked by Ga i and Ga q knockdown as well as by Ptx pretreatment. LPA increased GSK3b phosphorylation and b-catenin activation. LPA induced the cytosol to nuclear translocation of bcatenin, which was inhibited by PKC inhibitors. LPA stimulated the binding of b-catenin on the E-box located in the promoter of the CDH-1 gene and decreased CDH-1 promoter activity. In addition, the ATX and LPA-induced increase in hMSC migration was blocked by b-catenin siRNA transfection. LPA-induced PKC phosphorylation is also involved in Rac1 and CDC42 activation, and Rac1 and CDC42 knockdown abolished LPA-induced F-actin reorganization. In conclusion, ATX/LPA stimulates the migration of hMSCs through LPAR1/3-dependent E-cadherin reduction and cytoskeletal rearrangement via PKC/GSK3b/b-catenin and PKC/Rho GTPase pathways. STEM CELLS 2015;33:819-832

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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

Cited by 38 publications

References 78 publications

miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1

miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1

Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres

Autotaxin-LPA Axis Regulates hMSC Migration by Adherent Junction Disruption and Cytoskeletal Rearrangement Via LPAR1/3-Dependent PKC/GSK3β/β-Catenin and PKC/Rho GTPase Pathways

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