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Journal Article
Metabolic regulation of species-specific developmental rates
2023
Overview
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 development
1
–
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
Lb
NOX 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.
An in vitro system that recapitulates temporal characteristics of embryonic development demonstrates that the different rates of mouse and human embryonic development stem from differences in metabolic rates and—further downstream—the global rate of protein synthesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/100
/ 13/106
/ 13/31
/ 13/51
/ 14
/ 14/63
/ 38/35
/ 64/60
/ Animals
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryo, Mammalian - metabolism
/ Embryonic Development - physiology
/ Humanities and Social Sciences
/ Humans
/ Mice
/ NADH
/ Nicotinamide adenine dinucleotide
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Proteins
/ Science
