Single-cell profiling and SCOPE-seq reveal lineage dynamics of adult ventricular-subventricular zone neurogenesis and NOTUM as a key regulator Journal Article
| Authors: | Mizrak, D.; Bayin, N. S.; Yuan, J.; Liu, Z.; Suciu, R. M.; Niphakis, M. J.; Ngo, N.; Lum, K. M.; Cravatt, B. F.; Joyner, A. L.; Sims, P. A. |
| Article Title: | Single-cell profiling and SCOPE-seq reveal lineage dynamics of adult ventricular-subventricular zone neurogenesis and NOTUM as a key regulator |
| Abstract: | In the adult ventricular-subventricular zone (V-SVZ), neural stem cells (NSCs) generate new olfactory bulb (OB) neurons and glia throughout life. To map adult neuronal lineage progression, we profiled >56,000 V-SVZ and OB cells by single-cell RNA sequencing (scRNA-seq). Our analyses reveal the molecular diversity of OB neurons, including fate-mapped neurons, lineage progression dynamics, and an NSC intermediate enriched for Notum, which encodes a secreted WNT antagonist. SCOPE-seq technology, which links live-cell imaging with scRNA-seq, uncovers cell-size transitions during NSC differentiation and preferential NOTUM binding to proliferating neuronal precursors. Consistently, application of NOTUM protein in slice cultures and pharmacological inhibition of NOTUM in slice cultures and in vivo demonstrated that NOTUM negatively regulates V-SVZ proliferation. Timely, context-dependent neurogenesis demands adaptive signaling among neighboring progenitors. Our findings highlight a critical regulatory state during NSC activation marked by NOTUM, which attenuates WNT-stimulated proliferation in NSC progeny. © 2020 The Author(s) Mizrak et al. combine single-cell RNA-seq, SCOPE-seq, and genetic fate mapping to study adult olfactory bulb neurogenesis from the ventricular-subventricular zone (V-SVZ). They reveal the key molecular and cellular changes during neuronal lineage differentiation and highlight an activating NSC intermediate marked by Notum, an extracellular signal that controls V-SVZ proliferation. © 2020 The Author(s) |
| Keywords: | signal transduction; adult; controlled study; protein expression; unclassified drug; nonhuman; cell proliferation; animal cell; mouse; animal tissue; protein binding; cell fate; in vivo study; neural stem cell; subventricular zone; cell lineage; glia cell; cell size; nerve cell differentiation; wnt protein; olfactory bulb; regulator protein; tissue culture; wnt signaling; single cell analysis; brain slice; notum; priority journal; article; rna sequencing; lineage tracing; adult neural stem cell; scope-seq; single cell rna-sequencing; ventricular-subventricular zone; notum protein |
| Journal Title: | Cell Reports |
| Volume: | 31 |
| Issue: | 12 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2020-06-23 |
| Start Page: | 107805 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2020.107805 |
| PUBMED: | 32579931 |
| PROVIDER: | scopus |
| PMCID: | PMC7396151 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
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