Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone

Abstract

BACKGROUND: The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate.

OBJECTIVE: This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ).

METHODS: A literature search was conducted using Pubmed including the keywords “ventricular-subventricular zone,” “neural stem cell,” “heterogeneity,” “identity” and/or “single cell” to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s).

RESULTS: This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type.

CONCLUSIONS: Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.

Keywords

ventricular-subventricular zone / neural stem cells / positional identity / single-cell / heterogeneity

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Compliance with ethics guidelines

The authors declare that they have no conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Acknowledgements

The authors thank the members of the Ihrie and Irish laboratories, Dr. Corey Harwell, Dr. Jan H. Lui and Dr. Arturo Álvarez-Buylla for thoughtful discussions. Work in the Ihrie laboratory is supported by a Research Grant from the Tuberous Sclerosis Alliance (R. A. I.), a Discovery Grant from the Vanderbilt-Ingram Cancer Center Ambassadors (R. A. I.), NIH/NINDS R01 NS096238-01, DOD W81XWH-16-1-0171/TS150037, and support through NIH 2T32CA009592-26 (G.V.R.) and Vanderbilt Clinical Neuroscience Scholars Program (G.V.R.).

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