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

Cell Stem Cell. 2015 Sep 3;17(3):360-72. doi: 10.1016/j.stem.2015.07.013. Epub 2015 Aug 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Databases as Topic
  • Dentate Gyrus / cytology
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Mice, Transgenic
  • Models, Biological
  • Molecular Dynamics Simulation
  • Neural Stem Cells / cytology
  • Neurogenesis*
  • Reproducibility of Results
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Transcription Factors / metabolism
  • Transcriptome / genetics
  • Up-Regulation / genetics


  • Transcription Factors

Associated data

  • GEO/GSE71485