Academic Appointments

All Publications

  • Ferroptosis inducers are a novel therapeutic approach for advanced prostate cancer. Cancer research Ghoochani, A. n., Hsu, E. C., Aslan, M. n., Rice, M. A., Nguyen, H. M., Brooks, J. D., Corey, E. n., Paulmurugan, R. n., Stoyanova, T. n. 2021


    Ferroptosis is a type of programmed cell death induced by the accumulation of lipid peroxidation and lipid reactive oxygen species (ROS) in cells. It has been recently demonstrated that cancer cells are vulnerable to ferroptosis inducers (FIN). However, the therapeutic potential of ferroptosis inducers in prostate cancer in pre-clinical settings has not been explored. In this study, we demonstrate that mediators of ferroptosis SLC7A11, SLC3A2 and GPX4 are expressed in treatment-resistant prostate cancer. We further demonstrate that treatment-resistant prostate cancer cells are sensitive to two ferroptosis inducers, erastin and RSL3. Treatment with erastin and RSL3 led to a significant decrease in prostate cancer cell growth and migration in vitro and significantly delayed the tumor growth of treatment-resistant prostate cancer in vivo, with no measurable side effects. Combination of erastin or RSL3 with standard-of-care second-generation anti-androgens for advanced prostate cancer halted prostate cancer cell growth and migration in vitro and tumor growth in vivo. These results demonstrate the potential of erastin or RSL3 independently and in combination with standard-of-care second-generation anti-androgens as novel therapeutic strategies for advanced prostate cancer.

    View details for DOI 10.1158/0008-5472.CAN-20-3477

    View details for PubMedID 33483372

  • MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis ONCOGENE Ghoochani, A., Schwarz, M. A., Yakubov, E., Engelhorn, T., Doerfler, A., Buchfelder, M., Bucala, R., Savaskan, N. E., Eyupoglu, I. Y. 2016; 35 (48): 6246-6261


    Microglial cells in the brain tumor microenvironment are associated with enhanced glioma malignancy. They persist in an immunosuppressive M2 state at the peritumoral site and promote the growth of gliomas. Here, we investigated the underlying factors contributing to the abolished immune surveillance. We show that brain tumors escape pro-inflammatory M1 conversion of microglia via CD74 activation through the secretion of the cytokine macrophage migration inhibitory factor (MIF), which results in a M2 shift of microglial cells. Interruption of this glioma-microglial interaction through an antibody-neutralizing approach or small interfering RNA (siRNA)-mediated inhibition prolongs survival time in glioma-implanted mice by reinstating the microglial pro-inflammatory M1 function. We show that MIF-CD74 signaling inhibits interferon (IFN)-γ secretion in microglia through phosphorylation of microglial ERK1/2 (extracellular signal-regulated protein kinases 1 and 2). The inhibition of MIF signaling or its receptor CD74 promotes IFN-γ release and amplifies tumor death either through pharmacological inhibition or through siRNA-mediated knockdown. The reinstated IFN-γ secretion leads both to direct inhibition of glioma growth as well as inducing a M2 to M1 shift in glioma-associated microglia. Our data reveal that interference with the MIF signaling pathway represents a viable therapeutic option for the restoration of IFN-γ-driven immune surveillance.

    View details for DOI 10.1038/onc.2016.160

    View details for Web of Science ID 000388857700009

    View details for PubMedID 27157615

  • A versatile ex vivo technique for assaying tumor angiogenesis and microglia in the brain ONCOTARGET Ghoochani, A., Yakubov, E., Sehm, T., Fan, Z., Hock, S., Buchfelder, M., Eyuepoglu, I. Y., Savaskan, N. E. 2016; 7 (2): 1838-1853


    Primary brain tumors are hallmarked for their destructive activity on the microenvironment and vasculature. However, solely few experimental techniques exist to access the tumor microenvironment under anatomical intact conditions with remaining cellular and extracellular composition. Here, we detail an ex vivo vascular glioma impact method (VOGIM) to investigate the influence of gliomas and chemotherapeutics on the tumor microenvironment and angiogenesis under conditions that closely resemble the in vivo situation. We generated organotypic brain slice cultures from rats and transgenic mice and implanted glioma cells expressing fluorescent reporter proteins. In the VOGIM, tumor-induced vessels presented the whole range of vascular pathologies and tumor zones as found in human primary brain tumor specimens. In contrast, non-transformed cells such as primary astrocytes do not alter the vessel architecture. Vascular characteristics with vessel branching, junctions and vessel meshes are quantitatively assessable as well as the peritumoral zone. In particular, the VOGIM resembles the brain tumor microenvironment with alterations of neurons, microglia and cell survival. Hence, this method allows live cell monitoring of virtually any fluorescence-reporter expressing cell. We further analyzed the vasculature and microglia under the influence of tumor cells and chemotherapeutics such as Temozolamide (Temodal/Temcad®). Noteworthy, temozolomide normalized vasculare junctions and branches as well as microglial distribution in tumor-implanted brains. Moreover, VOGIM can be facilitated for implementing the 3Rs in experimentations. In summary, the VOGIM represents a versatile and robust technique which allows the assessment of the brain tumor microenvironment with parameters such as angiogenesis, neuronal cell death and microglial activity at the morphological and quantitative level.

    View details for Web of Science ID 000369951100058

    View details for PubMedID 26673818

    View details for PubMedCentralID PMC4811501

  • Novel Aza-podophyllotoxin derivative induces oxidative phosphorylation and cell death via AMPK activation in triple-negative breast cancer. British journal of cancer Tailor, D. n., Going, C. C., Resendez, A. n., Kumar, V. n., Nambiar, D. K., Li, Y. n., Dheeraj, A. n., LaGory, E. L., Ghoochani, A. n., Birk, A. M., Stoyanova, T. n., Ye, J. n., Giaccia, A. J., Le, Q. T., Singh, R. P., Sledge, G. W., Pitteri, S. J., Malhotra, S. V. 2020


    To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions work via indirectly activating AMP-activated protein kinase (AMPK) to alter cellular metabolism in favour of oxidative phosphorylation over aerobic glycolysis. The effect of these drugs is dependent on glycaemic and insulin conditions.  Therefore, development of small molecules, which can activate AMPK, irrespective of the energy state, may be a better approach for triple-negative breast cancer (TNBC) treatment.Therapeutic effect of SU212 on TNBC cells was examined using in vitro and in vivo models.We developed and characterised the efficacy of novel AMPK activator (SU212) that selectively induces oxidative phosphorylation and decreases glycolysis in TNBC cells, while not affecting these pathways in normal cells.   SU212 accomplished this metabolic reprogramming by activating AMPK independent of energy stress and irrespective of the glycaemic/insulin state. This leads to mitotic phase arrest and apoptosis in TNBC cells. In vivo, SU212 inhibits tumour growth, cancer progression and metastasis.SU212 directly activates AMPK in TNBC cells, but does not hamper glucose metabolism in normal cells. Our study provides compelling preclinical data for further development of SU212 for the treatment of TNBC.

    View details for DOI 10.1038/s41416-020-01137-4

    View details for PubMedID 33139797

  • Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1. Proceedings of the National Academy of Sciences of the United States of America Hsu, E. C., Rice, M. A., Bermudez, A. n., Marques, F. J., Aslan, M. n., Liu, S. n., Ghoochani, A. n., Zhang, C. A., Chen, Y. S., Zlitni, A. n., Kumar, S. n., Nolley, R. n., Habte, F. n., Shen, M. n., Koul, K. n., Peehl, D. M., Zoubeidi, A. n., Gambhir, S. S., Kunder, C. A., Pitteri, S. J., Brooks, J. D., Stoyanova, T. n. 2020


    Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.

    View details for DOI 10.1073/pnas.1905384117

    View details for PubMedID 31932422

  • Loss of Notch1 Activity Inhibits Prostate Cancer Growth and Metastasis and Sensitizes Prostate Cancer Cells to Antiandrogen Therapies MOLECULAR CANCER THERAPEUTICS Rice, M. A., Hsu, E., Aslan, M., Ghoochani, A., Su, A., Stoyanova, T. 2019; 18 (7): 1230–42
  • Ameliorating the Effect of Pioglitazone on LPS-Induced Inflammation of Human Oligodendrocyte Progenitor Cells. Cellular and molecular neurobiology Peymani, M., Ghaedi, K., Hashemi, M., Ghoochani, A., Kiani-Esfahani, A., Nasr-Esfahani, M. H., Baharvand, H. 2017


    Oligodendrocyte progenitor cells (OPCs) are appropriate model cells for studying the progress of neurodegenerative disorders and evaluation of pharmacological efficacies of small molecules for treatment of these disorders. Here, we focused on the therapeutic role of Pioglitazone, which is a selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a respective nuclear receptor in inflammatory responses. Human embryonic stem cell-derived OPCs were pretreated by Pioglitazone at differing concentrations. Pretreated OPCs were further examined after induction of inflammation by LPS. Interestingly, Pioglitazone reversed the inflammatory conditions and enhanced OPC viability. Data showed that Pioglitazone reduced Nitric Oxide (NO) production. Moreover, Pioglitazone enhanced cell viability through distinct mechanisms including reduction of apoptosis and regulation of cell cycle markers. This study demonstrated that NO induces apoptosis through FOXO1 and degradation of β-catenin, while the presence of Pioglitazone inhibited these effects in rescuing human OPCs from apoptosis. Also, Pioglitazone did not show a significant influence on mRNA levels of TLR2, TRL4, and TNFα. Furthermore, simultaneous treatment of Pioglitazone with CHIR, a GSKβ inhibitor, facilitated anti-apoptotic responses of OPCs. Taken together, therapy with Pioglitazone represents a novel potential drug in alleviating the loss of OPCs in neurodegenerative conditions.

    View details for DOI 10.1007/s10571-017-0500-6

    View details for PubMedID 28488008

  • Plasticity Related Gene 3 (PRG3) overcomes myelin-associated growth inhibition and promotes functional recovery after spinal cord injury AGING-US Broggini, T., Schnell, L., Ghoochani, A., Mateos, J. M., Buchfelder, M., Wiendieck, K., Schaefer, M. K., Eyupoglu, I. Y., Savaskan, N. E. 2016; 8 (10): 2463-?


    The Plasticity Related Gene family covers five, brain-specific, transmembrane proteins (PRG1-5, also termed LPPR1-5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. In utero electroporation of PRG3 induced dendritic protrusions and accelerated spine formations in cortical pyramidal neurons. The neurite growth promoting activity of PRG3 requires RasGRF1 (RasGEF1/Cdc25) mediated downstream signaling. Moreover, in axon collapse assays, PRG3-induced neurites resisted growth inhibitors such as myelin, Nogo-A (Reticulon/RTN-4), thrombin and LPA and impeded the RhoA-Rock-PIP5K induced neurite repulsion. Transgenic adult mice with constitutive PRG3 expression displayed strong axonal sprouting distal to a spinal cord lesion. Moreover, fostered PRG3 expression promoted complex motor-behavioral recovery compared to wild type controls as revealed in the Schnell swim test (SST). Thus, PRG3 emerges as a developmental RasGRF1-dependent conductor of filopodia formation and axonal growth enhancer. PRG3-induced neurites resist brain injury-associated outgrowth inhibitors and contribute to functional recovery after spinal cord lesions. Here, we provide evidence that PRG3 operates as an essential neuronal growth promoter in the nervous system. Maintaining PRG3 expression in aging brain may turn back the developmental clock for neuronal regeneration and plasticity.

    View details for DOI 10.18632/aging.101066

    View details for Web of Science ID 000390311800018

    View details for PubMedID 27744421

    View details for PubMedCentralID PMC5115901

  • Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis. Oncotarget Ghoochani, A., Hatipoglu Majernik, G., Sehm, T., Wach, S., Buchfelder, M., Taubert, H., Eyupoglu, I. Y., Savaskan, N. 2016; 7 (25): 38306-38318


    Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.

    View details for DOI 10.18632/oncotarget.9439

    View details for PubMedID 27203678

    View details for PubMedCentralID PMC5122391

  • Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema ONCOTARGET Sehm, T., Fan, Z., Ghoochani, A., Rauh, M., Engelhorn, T., Minakaki, G., Doerfler, A., Klucken, J., Buchfelder, M., Eyuepoglu, I. Y., Savaskan, N. 2016; 7 (24): 36021-36033


    The glutamate transporter xCT (SCL7a11, system Xc-, SXC) is an emerging key player in glutamate/cysteine/glutathione homeostasis in the brain and in cancer. xCT expression correlates with the grade of malignancy. Here, we report on the use of the U.S. Food and Drug Administration and EMA-approved xCT inhibitor, sulfasalazine (SAS) in gliomas. SAS does not affect cell viability in gliomas at concentrations below 200 µM. At higher concentrations SAS becomes gliomatoxic. Mechanistically SAS inhibits xCT and induces ferroptotic cell death in glioma cells. There is no evidence for impact on autophagic flux following SAS application. However, SAS can potentiate the efficacy of the standard chemotherapeutic and autophagy-inducing agent temozolomide (Temcat, Temodal or Temodar®). We also investigated SAS in non-transformed cellular constituents of the brain. Neurons and brain tissue are almost non-responding to SAS whereas isolated astrocytes are less sensitive towards SAS toxicity compared to gliomas. In vivo SAS treatment does not affect experimental tumor growth and treated animals revealed comparable tumor volume as untreated controls. However, SAS treatment resulted in reduced glioma-derived edema and, hence, total tumor volume burden as revealed by T2-weighted magnetic resonance imaging. Altogether, we show that SAS can be utilized for targeting the glutamate antiporter xCT activity as a tumor microenvironment-normalizing drug, while crucial cytotoxic effects in brain tumors are minor.

    View details for DOI 10.18632/oncotarget.8651

    View details for Web of Science ID 000377756800042

    View details for PubMedID 27074570

    View details for PubMedCentralID PMC5094980

  • Hidden association of Cowden syndrome, PTEN mutation and meningioma frequency. Oncoscience Yakubov, E., Ghoochani, A., Buslei, R., Buchfelder, M., Eyüpoglu, I. Y., Savaskan, N. 2016; 3 (5-6): 149-155


    Cowden syndrome (CS) is clinically presented by multiple hamartomas, often with mucocutaneous lesions, goiter, breast cancer and gastrointestinal polyps. CS is a genetic disorder of autosomal dominant inheritance and is one distinct syndrome of the phosphatase and tensin homolog on chromosome 10 (PTEN) hamartoma tumor spectrum. Noteworthy, PTEN germline mutations are related to a wide range of brain tumors. We performed a systematic analysis and review of the medical literature for Cowden syndrome and meningioma and additionally present the case of a 29-year- old CS patient diagnosed with multiple meningiomas. We found strong evidence for high incidence of brain tumors in CS patients. In particular meningiomas and gangliocytomas/Lhermitte-Duclos disease were often associated with 8% and 9% respectively in CS patients. Since aberrations in chromosome 10q are associated with meningiomas, it is likely that the underlying mutations in CS drive to a certain extent neoplastic meningioma growth. We propose to include meningiomas and brain tumors in the major criteria spectrum of CS-related disorders. This could warrant early diagnosis of brain lesions and close therapy, as well as better monitoring of patients with CS.

    View details for DOI 10.18632/oncoscience.305

    View details for PubMedID 27489861

    View details for PubMedCentralID PMC4965257

  • The Synergistic Enhancement of Cloning Efficiency in Individualized Human Pluripotent Stem Cells by Peroxisome Proliferative-activated Receptor-? (PPAR?) Activation and Rho-associated Kinase (ROCK) Inhibition. journal of biological chemistry Kajabadi, N., Ghoochani, A., Peymani, M., Ghaedi, K., Kiani-Esfahani, A., Hashemi, M., Nasr-Esfahani, M. H., Baharvand, H. 2015; 290 (43): 26303-26313


    Although human pluripotent stem cells (hPSCs) provide valuable sources for regenerative medicine, their applicability is dependent on obtaining both suitable up-scaled and cost effective cultures. The Rho-associated kinase (ROCK) inhibitor Y-27632 permits hPSC survival upon dissociation; however, cloning efficiency is often still low. Here we have shown that pioglitazone, a selective peroxisome proliferative-activated receptor-γ agonist, along with Y-27632 synergistically diminished dissociation-induced apoptosis and increased cloning efficiency (2-3-fold versus Y-27632) without affecting pluripotency of hPSCs. Pioglitazone exerted its positive effect by inhibition of glycogen synthase kinase (GSK3) activity and enhancement of membranous β-catenin and E-cadherin proteins. These effects were reversed by GW-9662, an irreversible peroxisome proliferative-activated receptor-γ antagonist. This novel setting provided a step toward hPSC manipulation and its biomedical applications.

    View details for DOI 10.1074/jbc.M114.624841

    View details for PubMedID 26336103

    View details for PubMedCentralID PMC4646278

  • Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment CANCER SCIENCE Hatipoglu, G., Hock, S. W., Weiss, R., Fan, Z., Sehm, T., Ghoochani, A., Buchfelder, M., Savaskan, N. E., Eyuepoglu, I. Y. 2015; 106 (2): 160-170


    Malignant gliomas can be counted to the most devastating tumors in humans. Novel therapies do not achieve significant prolonged survival rates. The cancer cells have an impact on the surrounding vital tissue and form tumor zones, which make up the tumor microenvironment. We investigated the effects of sunitinib, a small molecule multitargeted receptor tyrosine kinase inhibitor, on constituents of the tumor microenvironment such as gliomas, astrocytes, endothelial cells, and neurons. Sunitinib has a known anti-angiogenic effect. We found that sunitinib normalizes the aberrant tumor-derived vasculature and reduces tumor vessel pathologies (i.e. auto-loops). Sunitinib has only minor effects on the normal, physiological, non-proliferating vasculature. We found that neurons and astrocytes are protected by sunitinib against glutamate-induced cell death, whereas sunitinib acts as a toxin towards proliferating endothelial cells and tumor vessels. Moreover, sunitinib is effective in inducing glioma cell death. We determined the underlying pathways by which sunitinib operates as a toxin on gliomas and found vascular endothelial growth factor receptor 2 (VEGFR2, KDR/Flk1) as the main target to execute gliomatoxicity. The apoptosis-inducing effect of sunitinib can be mimicked by inhibition of VEGFR2. Knockdown of VEGFR2 can, in part, foster the resistance of glioma cells to receptor tyrosine kinase inhibitors. Furthermore, sunitinib alleviates tumor-induced neurodegeneration. Hence, we tested whether temozolomide treatment could be potentiated by sunitinib application. Here we show that sunitinib can amplify the effects of temozolomide in glioma cells. Thus, our data indicate that combined treatment with temozolomide does not abrogate the effects of sunitinib. In conclusion, we found that sunitinib acts as a gliomatoxic agent and at the same time carries out neuroprotective effects, reducing tumor-induced neurodegeneration. Thus, this report uncovered sunitinib's actions on the brain tumor microenvironment, revealing novel aspects for adjuvant approaches and new clinical assessment criteria when applied to brain tumor patients.

    View details for DOI 10.1111/cas.12580

    View details for Web of Science ID 000350171000005

    View details for PubMedID 25458015

    View details for PubMedCentralID PMC4399021

  • Dual effects of peroxisome proliferator-activated receptor gamma on embryonic stem cell self-renewal in presence and absence of leukemia inhibitory factor EUROPEAN JOURNAL OF CELL BIOLOGY Peymani, M., Ghoochani, A., Ghaedi, K., Karamali, F., Karbalaie, K., Kiani-Esfahani, A., Rabiee, F., Nasr-Esfahani, M. H., Baharvand, H. 2013; 92 (4-5): 160-168


    The aim of this study was to evaluate the influence of peroxisome proliferator-activated receptor γ (PPARγ) on self-renewal of mouse embryonic stem cells (mESCs) in the presence and absence of leukemia inhibitory factor (LIF). We demonstrated that in the presence of LIF, the activation of PPARγ by Rosiglitazone led to an increased proliferation of mESCs whereas PPARγ antagonist (GW9662) reversed this effect. Additionally, upon PPARγ activation, LIF increased PPARγ expression and resulted in the degradation of suppressor of cytokine signaling 3 (SOCS3), an important negative regulator of LIF/signal transducers and activators of transcription 3 (STAT3)-pathway. In the absence of LIF, Rosiglitazone decreased proliferation of mESCs. In this state, our results showed that extracellular signal-regulated kinase (ERK) proteins were activated and resulted in the suppression of Nanog expression, an important pluripotency determinant, whereas it did not affect Oct4 expression. These results suggest that the pivotal role of PPARγ on mESC self-renewal depends on the presence and absence of LIF.

    View details for DOI 10.1016/j.ejcb.2013.03.003

    View details for Web of Science ID 000321174500004

    View details for PubMedID 23628590

  • The influence of peroxisome proliferator-activated receptor gamma(1) during differentiation of mouse embryonic stem cells to neural cells DIFFERENTIATION Ghoochani, A., Shabani, K., Peymani, M., Ghaedi, K., Karamali, F., Karbalaei, K., Tanhaie, S., Salamian, A., Esmaeili, A., Valian-Borujeni, S., Hashemi, M., Nasr-Esfahani, M. H., Baharvand, H. 2012; 83 (1): 60-67


    Peroxisome proliferator activated receptor γ, belongs to PPARs, which exerts various metabolic functions including differentiation process. To testify the importance of PPARγ in neural differentiation of mouse embryonic stem cells (mESCs), its expression level was assessed. Data revealed an elevation in expression level of PPARγ when neural precursors (NPs) are formed upon retinoic acid treatment. Thus, involvement of PPARγ in two stages of neural differentiation of mESCs, during and post-NPs formation was examined by application of its agonist and antagonist. Our results indicated that PPARγ inactivation via treatment with GW9662 during NPs formation, reduced expression of neural precursor and neural (neuronal and astrocytes) markers. However, PPARγ inactivation by antagonist treatment post-NPs formation stage only decreased the expression of mature astrocyte marker (Gfap) suggesting that inactivation of PPARγ by antagonist decreased astrocyte differentiation. Here, we have demonstrated the stage dependent role of PPARγ modulation on neural differentiation of mESCs by retinoic acid treatment for the first time.

    View details for DOI 10.1016/j.diff.2011.08.009

    View details for Web of Science ID 000297249700007

    View details for PubMedID 22099177