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Single-cell lineage tracing


Nestin-CreER; Confetti mouse brain

Single embryonic and adult neural stem/progenitor cells are characterized by their self-renewal and differentiation potential. Lineage tracing via clonal analysis allows for specific labeling of a single neural stem/progenitor cells and tracking of its progeny throughout developmental continuum. Over the past five decades, a plethora of clonal analysis methods have been developed in tandem with integration of chemical, genetic, imaging and sequencing techniques. Applications of these approaches have gained diverse insights into the heterogeneous behavior of neural stem/progenitor cells, lineage relationships between cells, molecular regulation of fate specification and ontogeny of complex neural tissues. Wu lab recently summarizes the history and methods of clonal analysis as well as highlight key findings revealed by single-cell lineage tracking of stem cells in developing and adult brains across different animal models.




There are multiple waves of technological innovation driving the development of clonal analysis in history.


The developmental history of clonal analysis

The classic clonal analysis method is to label a single founder cell and track its progeny over time by either snapshot-type endpoint analysis or real-time recording. We provide an overview of the genetic toolbox for clonal analysis:


1. Sparse retroviral library labeling for clonal analysis

2. . Genetic multicolor labeling for clonal analysis and time-lapse imaging

3. Inducible genetic sparse labeling for clonal analysis

4. Genomic editing of synthetic target arrays for clonal analysis



Multiplexed strategies for lineage tracing and clonal analysis


Clonal analysis has been applied to reveal the behavior of neural stem/progenitor cells in drosophila, zebrafish, mouse and non-human primate.


Our lab has recently used in vivo clonal analysis to reveal # spatiotemporal regulation of thalamic nucleogenesis #.


Refer to NEWS https://genwulab.wixsite.com/wulab/thalamic-nucleogenesis



Assistant investigator Dr. Jingjing Wang and graduate students Mingrui Xu, Xize Guo and Tingting Li contributed equally to the review.

The review article was published online in Cell Regeneration on October 12th, 2018  (https://doi.org/10.1016/j.cr.2018.09.001). The article is titled Illumination of neural development by in vivo clonal analysis.

This study was supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences Pilot Project A, and the State Key Laboratory of Molecular Developmental Biology.










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中国科学院遗传与发育生物学研究所

分子发育生物学国家重点实验室

中国科学院脑智卓越中心