To form fully functional four-chambered structure,mammalian heart development undergoes a transient finger-shaped trabeculae,crucial for efficient contraction and exchange for gas and nutrient.Although its development...To form fully functional four-chambered structure,mammalian heart development undergoes a transient finger-shaped trabeculae,crucial for efficient contraction and exchange for gas and nutrient.Although its developmental origin and direct relevance to congenital heart disease has been studied extensively,the time-resolved cellular mechanism underlying hypotrabeculation remains elusive.Here,we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h.Compared to control,hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms:both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration.Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner.Thus,our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.展开更多
基金the National Basic Research Program of China(Grants No.2019YFA0801802 and 2017YFA0103402)the National Natural Science Foundation of China(Grants No.32025015 and 31771607)the Peking-Tsinghua Center for Life Sciences,and the 1000 Youth Talents Program of China.We thank the Confocal LSM 710 Core at National Center for Protein Sciences at Peking University for technical help.
文摘To form fully functional four-chambered structure,mammalian heart development undergoes a transient finger-shaped trabeculae,crucial for efficient contraction and exchange for gas and nutrient.Although its developmental origin and direct relevance to congenital heart disease has been studied extensively,the time-resolved cellular mechanism underlying hypotrabeculation remains elusive.Here,we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h.Compared to control,hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms:both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration.Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner.Thus,our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.
