Metabolic regulation of species-specific developmental rates
Animals display substantial inter-species variation in the rate of embryonic development despite a broad conservation of the overall sequence of developmental events. Differences in biochemical reaction rates, including the rates of protein production and degradation, are thought to be responsible f...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147878 |
| _version_ | 1811087287237214208 |
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| author | Diaz-Cuadros, Margarete Miettinen, Teemu P Skinner, Owen S Sheedy, Dylan Díaz-García, Carlos Manlio Gapon, Svetlana Hubaud, Alexis Yellen, Gary Manalis, Scott R Oldham, William M Pourquié, Olivier |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Diaz-Cuadros, Margarete Miettinen, Teemu P Skinner, Owen S Sheedy, Dylan Díaz-García, Carlos Manlio Gapon, Svetlana Hubaud, Alexis Yellen, Gary Manalis, Scott R Oldham, William M Pourquié, Olivier |
| author_sort | Diaz-Cuadros, Margarete |
| collection | MIT |
| description | Animals display substantial inter-species variation in the rate of embryonic development despite a broad conservation of the overall sequence of developmental events. Differences in biochemical reaction rates, including the rates of protein production and degradation, are thought to be responsible for species-specific rates of development1-3. However, the cause of differential biochemical reaction rates between species remains unknown. Here, using pluripotent stem cells, we have established an in vitro system that recapitulates the twofold difference in developmental rate between mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we show that mass-specific metabolic rates scale with the developmental rate and are therefore higher in mouse cells than in human cells. Reducing these metabolic rates by inhibiting the electron transport chain slowed down the segmentation clock by impairing the cellular NAD+/NADH redox balance and, further downstream, lowering the global rate of protein synthesis. Conversely, increasing the NAD+/NADH ratio in human cells by overexpression of the Lactobacillus brevis NADH oxidase LbNOX increased the translation rate and accelerated the segmentation clock. These findings represent a starting point for the manipulation of developmental rate, with multiple translational applications including accelerating the differentiation of human pluripotent stem cells for disease modelling and cell-based therapies. |
| first_indexed | 2024-09-23T13:43:02Z |
| format | Article |
| id | mit-1721.1/147878 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:43:02Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1478782023-02-04T03:21:54Z Metabolic regulation of species-specific developmental rates Diaz-Cuadros, Margarete Miettinen, Teemu P Skinner, Owen S Sheedy, Dylan Díaz-García, Carlos Manlio Gapon, Svetlana Hubaud, Alexis Yellen, Gary Manalis, Scott R Oldham, William M Pourquié, Olivier Massachusetts Institute of Technology. Department of Biological Engineering Animals display substantial inter-species variation in the rate of embryonic development despite a broad conservation of the overall sequence of developmental events. Differences in biochemical reaction rates, including the rates of protein production and degradation, are thought to be responsible for species-specific rates of development1-3. However, the cause of differential biochemical reaction rates between species remains unknown. Here, using pluripotent stem cells, we have established an in vitro system that recapitulates the twofold difference in developmental rate between mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we show that mass-specific metabolic rates scale with the developmental rate and are therefore higher in mouse cells than in human cells. Reducing these metabolic rates by inhibiting the electron transport chain slowed down the segmentation clock by impairing the cellular NAD+/NADH redox balance and, further downstream, lowering the global rate of protein synthesis. Conversely, increasing the NAD+/NADH ratio in human cells by overexpression of the Lactobacillus brevis NADH oxidase LbNOX increased the translation rate and accelerated the segmentation clock. These findings represent a starting point for the manipulation of developmental rate, with multiple translational applications including accelerating the differentiation of human pluripotent stem cells for disease modelling and cell-based therapies. 2023-02-03T19:51:13Z 2023-02-03T19:51:13Z 2023-01-19 2023-02-03T19:45:30Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147878 Diaz-Cuadros, Margarete, Miettinen, Teemu P, Skinner, Owen S, Sheedy, Dylan, Díaz-García, Carlos Manlio et al. 2023. "Metabolic regulation of species-specific developmental rates." Nature, 613 (7944). en 10.1038/s41586-022-05574-4 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC bioRxiv |
| spellingShingle | Diaz-Cuadros, Margarete Miettinen, Teemu P Skinner, Owen S Sheedy, Dylan Díaz-García, Carlos Manlio Gapon, Svetlana Hubaud, Alexis Yellen, Gary Manalis, Scott R Oldham, William M Pourquié, Olivier Metabolic regulation of species-specific developmental rates |
| title | Metabolic regulation of species-specific developmental rates |
| title_full | Metabolic regulation of species-specific developmental rates |
| title_fullStr | Metabolic regulation of species-specific developmental rates |
| title_full_unstemmed | Metabolic regulation of species-specific developmental rates |
| title_short | Metabolic regulation of species-specific developmental rates |
| title_sort | metabolic regulation of species specific developmental rates |
| url | https://hdl.handle.net/1721.1/147878 |
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