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 |