Title Continuous live imaging reveals a subtle pathological alteration with cell behaviors in congenital heart malformation
Authors Li, Xin
Yue, Yanzhu
Zhang, Youdong
Liao, Yuanhui
Wang, Qianhao
Bian, Yunkun
Na, Jie
He, Aibin
Affiliation Peking Univ, Coll Future Technol, Peking Tsinghua Ctr Life Sci, Inst Mol Med,Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China
Peking Univ, Sch Software & Microelect, Beijing 100871, Peoples R China
Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, Sch Med, Beijing 100084, Peoples R China
Keywords LIGHT-SHEET MICROSCOPY
ONE-STEP GENERATION
CARDIOMYOCYTE PROLIFERATION
FLUORESCENCE MICROSCOPY
CARDIAC DEVELOPMENT
CHAMBER FORMATION
MICE
RECONSTRUCTION
MORPHOGENESIS
GENETICS
Issue Date Jan-2022
Publisher FUNDAMENTAL RESEARCH
Abstract 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 recon-structed 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.
URI http://hdl.handle.net/20.500.11897/654633
ISSN 2096-9457
DOI 10.1016/j.fmre.2021.11.025
Indexed ESCI
Appears in Collections: 分子医学研究所
软件与微电子学院

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