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 Nauen, Kimberly M. Christian, Guo Li Ming, Hongjun Song

Research output: Contribution to journalArticle

Abstract

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 (US)
Article number1817
Pages (from-to)360-372
Number of pages13
JournalCell Stem Cell
Volume17
Issue number3
DOIs
StatePublished - Sep 3 2015

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Neural Stem Cells
Neurogenesis
RNA
Single-Cell Analysis
Biological Phenomena
Adult Stem Cells
Protein Biosynthesis
Computational Biology
Transcriptome
Energy Metabolism
Regeneration
Homeostasis
Transcription Factors
Stem Cells
Gene Expression

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Shin, J., Berg, D. A., Zhu, Y., Shin, J. Y., Song, J., Bonaguidi, M. A., ... Song, H. (2015). Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis. Cell Stem Cell, 17(3), 360-372. [1817]. https://doi.org/10.1016/j.stem.2015.07.013

Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis. / Shin, Jaehoon; Berg, Daniel A.; Zhu, Yunhua; Shin, Joseph Y.; Song, Juan; Bonaguidi, Michael A.; Enikolopov, Grigori; Nauen, David; Christian, Kimberly M.; Ming, Guo Li; Song, Hongjun.

In: Cell Stem Cell, Vol. 17, No. 3, 1817, 03.09.2015, p. 360-372.

Research output: Contribution to journalArticle

Shin, J, Berg, DA, Zhu, Y, Shin, JY, Song, J, Bonaguidi, MA, Enikolopov, G, Nauen, D, Christian, KM, Ming, GL & Song, H 2015, 'Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis', Cell Stem Cell, vol. 17, no. 3, 1817, pp. 360-372. https://doi.org/10.1016/j.stem.2015.07.013
Shin, Jaehoon ; Berg, Daniel A. ; Zhu, Yunhua ; Shin, Joseph Y. ; Song, Juan ; Bonaguidi, Michael A. ; Enikolopov, Grigori ; Nauen, David ; Christian, Kimberly M. ; Ming, Guo Li ; Song, Hongjun. / Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis. In: Cell Stem Cell. 2015 ; Vol. 17, No. 3. pp. 360-372.
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