Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis

Jaehoon Shin, Daniel A. Berg, Yunhua Zhu, Joseph Y. Shin, Juan Song, Michael A. Bonaguidi, Grigori Enikolopov, David W. Nauen, Kimberly M. Christian, Guo Li Ming, Hongjun Song*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

522 Citations (Scopus)


Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic pipeline, to statistically quantify singe-cell gene expression along a de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of adult qNSCs, characterized by active niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes.

Original languageEnglish
Pages (from-to)360-372
Number of pages13
JournalCell Stem Cell
Issue number3
Early online date20 Aug 2015
Publication statusPublished - 3 Sept 2015

Bibliographical note

Acknowledgments: We thank S.L. Salzberg, H.H. Kazazian, and B. Langmead for suggestions; members of Song and Ming laboratories for discussion; and Y. Cai and L. Liu for technical support. This work was supported by MSCRF to H.S. and G.L.M., the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation to G.L.M, a fellowship from Samsung to J. Shin, and an EMBO long-term postdoctoral fellowship and a grant from Swedish Research Council to D.A.B.


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