TY - JOUR
T1 - Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis
AU - Shin, Jaehoon
AU - Berg, Daniel A.
AU - Zhu, Yunhua
AU - Shin, Joseph Y.
AU - Song, Juan
AU - Bonaguidi, Michael A.
AU - Enikolopov, Grigori
AU - Nauen, David W.
AU - Christian, Kimberly M.
AU - Ming, Guo Li
AU - Song, Hongjun
N1 - 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.
PY - 2015/9/3
Y1 - 2015/9/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941010341&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2015.07.013
DO - 10.1016/j.stem.2015.07.013
M3 - Article
C2 - 26299571
AN - SCOPUS:84941010341
SN - 1934-5909
VL - 17
SP - 360
EP - 372
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -
