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Expression data from human induced pluripotent stem cell-derived teratomas and embryoid bodies

ABSTRACT: The tumorigenicity of human pluripotent stem cells (hPSCs) is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a specific cell surface marker of hPSCs that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for hPSC survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and clostridium perfringens enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of hPSC-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated hPSCs from culture, highlighting a strategy that may increase the safety of hPSC-based cell therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38088 | GEO | 2013/06/01

SECONDARY ACCESSION(S): PRJNA167173

REPOSITORIES: GEO

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Project description:Human pancreatic stellate cells (HPSCs) are an essential stromal component and are the mediators of pancreatic ductal adenocarcinoma (PDAC) progression. Small extracellular vesicles (sEVs) are membrane-enclosed nanoparticles released from stellate cells adjacent to the PDAC. sEVs are believed to play a key role in cell-cell communications and may play a critical role in disease progression. The role of membrane proteins of HPSC sEVs in the PDAC tumor microenvironment is unclear and to date, there has not been a quantitative proteomic comparison of sEVs from normal pancreatic stellate cells (HPaStec) and from PDAC-associated stellate cells (HPSCs). We hypothesized there would be differences in sEVs secretion and membrane protein expression between the 2 conditions that might contribute to PDAC biology. To test these hypotheses, we isolated sEVs using ultracentrifugation followed by characterization by electron microscopy and Nanoparticle Tracking Analysis. HPSCs secreted more sEVs compared to HPaStec, and these sEVs were enriched with exosomal markers, which was confirmed by Western blotting and flow cytometry. HPSC-sEVs also restore the activation of normal stellate cells. Next, we showed that intact membrane-associated proteins may be essential for sufficient uptake of stellate cell sEVs by both normal epithelial and cancer cells. Importantly, we demonstrated that stellate cells in general modulate the cellular proliferations of pancreatic cancer cells although stellate cell sEVs did not change the proliferation of cancer cells. We then compared sEV proteins isolated from HPSCs and HPaStecs cells using liquid chromatography–tandem mass spectrometry. Most of the 1,481 protein groups identified were shared with the exosome database, ExoCarta (http://exocarta.org/; curated by the Mathivanan Lab). Eighty-seven protein groups were differentially expressed (selected by 2-fold difference and adjusted P value ≤ 0.05) between HPSC and HPaStec sEVs. HPSC sEVs contained dramatically more CSE1L, a poor prognostic marker for pancreatic cancer. In conclusion, our findings using mass spectrometry–based proteomics may direct further studies to understand the biology and role of protein composition of HPSC sEVs in PDAC progression or to develop novel strategies based on delivery of exosome cargo to PDAC tumor cells.

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Expression data from human induced pluripotent stem cell-derived teratomas and embryoid bodies

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