Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response

Romanova N, Schmitz J, Strakeljahn M, Grünberger A, Bahnemann J, Noll T (2022)
Cells 11(11): 1763.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
Hyperosmolality can occur during industrial fed-batch cultivation processes of Chinese hamster ovary (CHO) cells as highly concentrated feed and base solutions are added to replenish nutrients and regulate pH values. Some effects of hyperosmolality, such as increased cell size and growth inhibition, have been elucidated by previous research, but the impact of hyperosmolality and the specific effects of the added osmotic-active reagents have rarely been disentangled. In this study, CHO cells were exposed to four osmotic conditions between 300 mOsm/kg (physiologic condition) and 530 mOsm/kg (extreme hyperosmolality) caused by the addition of either high-glucose-supplemented industrial feed or mannitol as an osmotic control. We present novel single-cell cultivation data revealing heterogeneity in mass gain and cell division in response to these treatments. Exposure to extreme mannitol-induced hyperosmolality and to high-glucose-oversupplemented feed causes cell cycle termination, mtDNA damage, and mitochondrial membrane depolarization, which hints at the onset of premature stress-induced senescence. Thus, this study shows that both mannitol-induced hyperosmolality (530 mOsm/kg) and glucose overfeeding induce severe negative effects on cell growth and mitochondrial activity; therefore, they need to be considered during process development for commercial production.
Stichworte
CHO; hyperosmolality; single-cell analysis; mitochondria
Erscheinungsjahr
2022
Zeitschriftentitel
Cells
Band
11
Ausgabe
11
Art.-Nr.
1763
eISSN
2073-4409
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2963556

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Romanova N, Schmitz J, Strakeljahn M, Grünberger A, Bahnemann J, Noll T. Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response. Cells. 2022;11(11): 1763.
Romanova, N., Schmitz, J., Strakeljahn, M., Grünberger, A., Bahnemann, J., & Noll, T. (2022). Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response. Cells, 11(11), 1763. https://doi.org/10.3390/cells11111763
Romanova, N., Schmitz, J., Strakeljahn, M., Grünberger, A., Bahnemann, J., and Noll, T. (2022). Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response. Cells 11:1763.
Romanova, N., et al., 2022. Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response. Cells, 11(11): 1763.
N. Romanova, et al., “Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response”, Cells, vol. 11, 2022, : 1763.
Romanova, N., Schmitz, J., Strakeljahn, M., Grünberger, A., Bahnemann, J., Noll, T.: Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response. Cells. 11, : 1763 (2022).
Romanova, Nadiya, Schmitz, Julian, Strakeljahn, Marie, Grünberger, Alexander, Bahnemann, Janina, and Noll, Thomas. “Single-Cell Analysis of CHO Cells Reveals Clonal Heterogeneity in Hyperosmolality-Induced Stress Response”. Cells 11.11 (2022): 1763.
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2022-06-02T07:18:01Z
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