Sendai virus‐mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor that originates from multipotent neural crest cells. NB cell populations that express embryonic stem cell-associated genes have been identified and shown to retain a multipotent phenotype. However, whether somatic reprogramming of NB cells can produce similar stem-cell like populations is unknown. Here, we sought to reprogram NB cell lines using an integration-free Sendai virus vector system. Of four NB cell lines examined, only SH-IN cells formed induced pluripotent stem cell-like colonies (SH-IN 4F colonies) at approximately 6 weeks following transduction. These SH-IN 4F colonies were alkaline phosphatase-positive. Array comparative genomic hybridization analysis indicated identical genomic aberrations in the SH-IN 4F cells as in the parental cells. SH-IN 4F cells had the ability to differentiate into the three embryonic germ layers in vitro, but rather formed NBs in vivo. Furthermore, SH-IN 4F cells exhibited resistance to cisplatin treatment and differentiated into endothelial-like cells expressing CD31 in the presence of vascular endothelial growth factor. These results suggest that SH-IN 4F cells are partially reprogrammed NB cells, and could be a suitable model for investigating the plasticity of aggressive tumors.

An Alternate Approach to Generate Induced Pluripotent Stem Cells with Precise CRISPR/Cas9 Tool

“…The generation of iPSCs from primary (HDFs) as well as cancerous cells (HEK293T) by using the current approach supports its reproducibility and broader-applicability. In order to understand the mechanism of cancer progression [ 82 , 83 ], reprogramming has been done for multiple cancerous cell lines including CHLA-10 [ 84 ], SH-IN [ 85 ], MCF-7 [ 86 ], A549 [ 87 ], and HEK293 [ 88 ]. Our strategy can be adopted to reprogram cancerous cell line (for instance, HEK293T) into iPSCs.…”

Protein-coding potential of RNAs measured by potentially translated island scores

“…MYCN directly stimulates NCYM and OCT4 transcription, whereas OCT4 induces MYCN (Kaneko et al 2015). This functional interplay forms a positive feedback loop, allowing these genes to induce each other's expression in human neuroblastomas (Suenaga et al 2014;Islam et al 2015;Kaneko et al 2015;Shoji et al 2015). Functional annotation of noncoding genes without putative domains was related to transcriptional regulation, and the target genes of transcription factors, including MYCN, TGIF, and ZIC2, were (Kaiser et al 2021).…”

Application of Cancer Cell Reprogramming Technology to Human Cancer Research

“…The reactivation of some tumor-suppressor genes, such as p16 Ink4a , in iPSCs might lead to increasing chemosensitivity as well as the repressing proliferation and invasiveness in reprogrammed cancer cells (30). Although not all cancer reprogramming studies have analyzed the tumorigenic potential or drug responsiveness of the resulting iPSCs (31,42,53), the results of studies contradict the outcomes of Miyoshi et al (30).…”