Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling
Abstract Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to dif...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202307554 |
| _version_ | 1797305177841074176 |
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| author | Jonathan Sai‐Hong Chui Teresa Izuel‐Idoype Alessandra Qualizza Rita Pires deAlmeida Lindsey Piessens Bernard K. van derVeer Gert Vanmarcke Aneta Malesa Paraskevi Athanasouli Ruben Boon Joris Vriens Leo vanGrunsven Kian Peng Koh Catherine M. Verfaillie Frederic Lluis |
| author_facet | Jonathan Sai‐Hong Chui Teresa Izuel‐Idoype Alessandra Qualizza Rita Pires deAlmeida Lindsey Piessens Bernard K. van derVeer Gert Vanmarcke Aneta Malesa Paraskevi Athanasouli Ruben Boon Joris Vriens Leo vanGrunsven Kian Peng Koh Catherine M. Verfaillie Frederic Lluis |
| author_sort | Jonathan Sai‐Hong Chui |
| collection | DOAJ |
| description | Abstract Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53‐independent quiescent state in immature hepatoma cells and in pluripotent stem cell‐derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity‐regulated growth arrest followed by cell maturation, mediated by activation of NF‐κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long‐term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely. |
| first_indexed | 2024-03-08T00:21:21Z |
| format | Article |
| id | doaj.art-d3f33e15b1534ffcbb0747b487db0584 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T00:21:21Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-d3f33e15b1534ffcbb0747b487db05842024-02-16T08:29:37ZengWileyAdvanced Science2198-38442024-02-01117n/an/a10.1002/advs.202307554Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT SignalingJonathan Sai‐Hong Chui0Teresa Izuel‐Idoype1Alessandra Qualizza2Rita Pires deAlmeida3Lindsey Piessens4Bernard K. van derVeer5Gert Vanmarcke6Aneta Malesa7Paraskevi Athanasouli8Ruben Boon9Joris Vriens10Leo vanGrunsven11Kian Peng Koh12Catherine M. Verfaillie13Frederic Lluis14KU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumLaboratory of Endometrium, Endometriosis and Reproductive Medicine Department of Development and Regeneration KU Leuven Herestraat 49 Leuven 3000 BelgiumLiver Cell Biology Research Group Vrije Universiteit Brussel Laarbeeklaan 103 Brussels 1090 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumKU Leuven Department of Development and Regeneration Stem Cell Institute Herestraat 49 Leuven 3000 BelgiumAbstract Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53‐independent quiescent state in immature hepatoma cells and in pluripotent stem cell‐derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity‐regulated growth arrest followed by cell maturation, mediated by activation of NF‐κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long‐term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely.https://doi.org/10.1002/advs.202307554hepatic modelstem cell differentiationcell cycleWNT signalingNF‐kB signaling |
| spellingShingle | Jonathan Sai‐Hong Chui Teresa Izuel‐Idoype Alessandra Qualizza Rita Pires deAlmeida Lindsey Piessens Bernard K. van derVeer Gert Vanmarcke Aneta Malesa Paraskevi Athanasouli Ruben Boon Joris Vriens Leo vanGrunsven Kian Peng Koh Catherine M. Verfaillie Frederic Lluis Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling Advanced Science hepatic model stem cell differentiation cell cycle WNT signaling NF‐kB signaling |
| title | Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling |
| title_full | Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling |
| title_fullStr | Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling |
| title_full_unstemmed | Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling |
| title_short | Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling |
| title_sort | osmolar modulation drives reversible cell cycle exit and human pluripotent cell differentiation via nf κв and wnt signaling |
| topic | hepatic model stem cell differentiation cell cycle WNT signaling NF‐kB signaling |
| url | https://doi.org/10.1002/advs.202307554 |
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