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Lisa Gesumaria



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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-05 - Comparative Transcriptomic Analysis of Lung-iPSC, NSCLC, and SCLC: Potential Implications for iPSC Modeling of Lung Cancer (ID 14212)

      12:00 - 13:30  |  Author(s): Lisa Gesumaria

      • Abstract
      • Slides

      Background

      In addition to having broad applicability as cellular therapies in regenerative medicine, transplantation and oncology, induced pluripotent stem cells (iPSC) may be useful models for studying a variety of benign and malignant diseases. Presently, limited information is available pertaining to the potential utility of iPSC for investigating epigenetic mechanisms of pulmonary carcinogenesis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the present study, RNA- seq techniques were used to examine gene expression profiles in 2 lung-iPSC (Lu-iPSC) clonesderived from normal human small airway epithelial cells (SAEC), 10 SCLC lines, and 10 NSCLC lines relative to SAEC.

      4c3880bb027f159e801041b1021e88e8 Result

      Using criteria of 2 fold change and FDR< 0.05, 6318, 12051, and 6504 genes were differentially expressed in Lu-iPSC, SCLC, and NSCLC lines, respectively. A substantial number of differentially expressed genes (44% total) in Lu-iPSC were unique to these cells. Approximately 1/3rdof genes differentially regulated in Lu-iPSC were modulated in a histology specific manner. 1515 genes representing 24%, 12%, and 23% of differentially expressed genes in Lu-iPSC, SCLC, and NSCLC lines, respectively, were commonly regulated across Lu-iPSC, SCLC and NSCLC. Top canonical pathways included cell cycle control of chromosomal replication and mitotic roles of Polo-like kinases (up-regulated), and granulocyte adhesion and role of cytokines in mediating communication between immune cells (down-regulated). 3499 genes were uniquely regulated in SCLC and NSCLC. 1937 genes were uniquely modulated in SCLC and Lu-iPSC; top canonical pathways included GABA receptor signaling and CREB signaling in neurons (up-regulated), and TREM1 signaling and IL-15 production (down-regulated). Only 102 genes were uniquely modulated in Lu-iPSC and NSCLC; top canonical pathways included tight junction signaling and hepatic fibrosis/hepatic stellate cell activation (up-regulated) and neurotrophin/TRK signaling and PTEN signaling (down-regulated). Differential gene expression signatures and associated pathways suggested that Lu-iPSC more closely reflect SCLC rather than NSCLC. To further examine similarities in epigenetic regulation of gene expression in Lu-iPSC and lung cancers, RNA-seq was performed on Lu-iPSC grown in the presence or absence of Decitabine (0.1┬ÁM x 72h). Expression levels of 885 genes were significantly altered by DAC; inflammatory cascades predominated the top canonical pathways. Additional pathways included nuclear excision repair, cell cycle control, DNA methylation and transcriptional repression, and transcriptional regulation of stem cells.DAC-mediated gene signatures in Lu-iPSC did not appear to overlap with SCLC or NSCLC signatures.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Collectively, these findings have potential implications regarding the use of Lu-iPSC models for examining lung cancer associated epigenetic events, and the development of epigenetic regimens for lung cancer therapy.

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