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Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning

Yagi, H.; Cui, C.; Saydmohammed, M.; Gabriel, G.; Baker, C.; Devine, W.; Wu, Y.; Lin, J.-h.; Malek, M.; Bais, A.; Murray, S.; Aronow, B. J.; Tsang, M. J.; Kostka, D.; Lo, C. W.

2023-04-21 developmental biology
10.1101/2023.04.21.537827 bioRxiv
Show abstract

Left-right patterning disturbance can cause severe birth defects, but it remains least understood of the three body axes. We uncovered an unexpected role for metabolic regulation in left-right patterning. Analysis of the first spatial transcriptome profile of left-right patterning revealed global activation of glycolysis, accompanied by right-sided expression of Bmp7 and genes regulating insulin growth factor signaling. Cardiomyocyte differentiation was left-biased, which may underlie the specification of heart looping orientation. This is consistent with known Bmp7 stimulation of glycolysis and glycolysis suppression of cardiomyocyte differentiation. Liver/lung laterality may be specified via similar metabolic regulation of endoderm differentiation. Myo1d, found to be left-sided, was shown to regulate gut looping in mice, zebrafish, and human. Together these findings indicate metabolic regulation of left-right patterning. This could underlie high incidence of heterotaxy-related birth defects in maternal diabetes, and the association of PFKP, allosteric enzyme regulating glycolysis, with heterotaxy. This transcriptome dataset will be invaluable for interrogating birth defects involving laterality disturbance.

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