Dual genetic tracing demonstrates the heterogeneous differentiation and function of neuromesodermal progenitors in vivo
Abstract
In recent decades, the traditional paradigm of three distinct germ layers formed during gastrulation has been revised with the identification of neuromesodermal progenitors (NMPs). These progenitors emerge during gastrulation and contribute to both the neural ectoderm, particularly the spinal cord, and the adjacent paraxial mesoderm [D. Henrique et al. , Development 142 , 2864–2875 (2015); R. J. Garriock et al. , Development 142 , 1628–1638 (2015); E. Tzouanacou et al. , Dev. Cell 17 , 365–376 (2009)]. However, effective genetic tools for lineage tracing and functional assessments of NMPs in vivo are currently lacking. Here, we developed a dual recombinase–mediated genetic system to specifically trace and ablate Brachyury + Sox2 + NMPs. Our genetic tracing and single-cell RNA sequencing analyses revealed that NMPs consist of three distinct unipotent and bipotent progenitor populations that progressively differentiate into neural and mesodermal fates. Genetic depletion of NMPs demonstrated their critical role in trunk and tail formation. This study provides in vivo genetic evidence supporting the heterogeneity of NMPs in terms of cell fate determination and their functional roles in the developing embryo.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (9)
Hengwei Jin
Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Zixin Liu
Tsinghua University , , ,
Jialing Mou
Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Muxue Tang
Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Xiuzhen Huang
Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Kuo Liu
State Key Laboratory of Mesoscience and Process Engineering, Institute of Process Engineering
Qianyu Zhang
College of Materials Science and Engineering
Kathy O. Lui
CAS CEMCS-CUHK Joint Laboratories, Department of Chemical Pathology, and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong
Bin Zhou