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Expression of SSEA-4 and Oct-4 from somatic cells in primary mouse gastric cell culture induced by brief strong acid

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Abstract

Environmental changes can stress and alter biology at the molecular and cellular level. For example, metal–protein interaction is a classic physic and biological property of nature, which is fundamentally influenced by acidity. Here, we report a unique cellular reprogramming phenomenon in that a brief strong acid treatment induced the expression of pluripotent stem cell (PSC) markers. We used strong acid to briefly challenge mix-cultured gastric cells, and then subcultured survived cells in a normal cell culture medium. We found that survival acid-treated cells expressed PSC markers detected by commonly used pluripotent antibodies such as SSEA-4 and Oct4. In addition, we observed that the survived cells from the acid challenge grew faster during the second and third weeks of subculture and had a relative short doubling time (DT) than the controls. PSC marker-labeled ‘older’ cells also presented immature cell-like morphology with some having marker Oct4 in the nucleus. Finally, the expression of the markers appeared to be sensitive to metal ion chelation. Removal of the metals during a brief acid treatment reduced pluripotent marker-positive cells, suggesting the dissociation of metals from metal-binding proteins may be a factor involved in the induction of stem cell markers. Our findings reveal that somatic cells appear to possess a plasticity feature to express pluripotent marker proteins or to select cell subpopulations that express pluripotent marker proteins when cells are transiently exposed to strong acid. It opens new directions for understanding conserved regulatory mechanisms involved in cellular survival under stressful stimulation.

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Acknowledgements

The authors would like to thank the Osteopathic Heritage Foundations, Graduate Studies Assistance Program at Ohio University Heritage College of Osteopathic Medicine for supporting graduate student YH.

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Authors and Affiliations

  1. Molecular & Cellular Biology Graduate Program, Departments of Biological Sciences and Biomedical Sciences, Ohio University, Athens, OH, 45701, USA

    Yuli Hu & Yang V. Li

  2. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, 346 Irvine Hall, Athens, OH, 45701, USA

    Yang V. Li

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  1. Yuli Hu
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YH performed the experiments and collected the data. YVL conceived and designed the study. All authors analyzed the data, interpreted results, and wrote and revised the manuscript.

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Correspondence to Yang V. Li.

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Hu, Y., Li, Y.V. Expression of SSEA-4 and Oct-4 from somatic cells in primary mouse gastric cell culture induced by brief strong acid. Mol Cell Biochem 476, 2813–2821 (2021). https://doi.org/10.1007/s11010-021-04124-2

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