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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

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Frontiers in Biology  2016, Vol. 11 Issue (4): 261-284   https://doi.org/10.1007/s11515-016-1407-1
  本期目录
Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone
Gabrielle Rushing1,Rebecca A. Ihrie2,*()
1. Program in Neuroscience, Vanderbilt University, Nashville, TN 37232, USA
2. Departments of Cancer Biology and Neurological Surgery, Vanderbilt University, Nashville, TN 37232, USA
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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.
Key words： ventricular-subventricular zone    neural stem cells    positional identity    single-cell    heterogeneity
收稿日期: 2016-04-22      出版日期: 2016-08-30
Corresponding Author(s): Rebecca A. Ihrie   
 引用本文:   
. [J]. Frontiers in Biology, 2016, 11(4): 261-284.
Gabrielle Rushing,Rebecca A. Ihrie. Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone. Front. Biol., 2016, 11(4): 261-284.
 链接本文:  
https://academic.hep.com.cn/fib/CN/10.1007/s11515-016-1407-1
https://academic.hep.com.cn/fib/CN/Y2016/V11/I4/261
Marker Cell type labeled Source
Alpha 6 integrin Activated B1 cells C cells Ramalho-Santos et al., 2002; Kokovay et al., 2010
Brain lipid binding protein (BLBP) Radial glia Activated B1 cells Feng et al., 1994; Doetsch, 2003; Kriegstein and Gotz, 2003Giachino et al., 2014
CD44 Astrocyte-restricted precursor cells Liu et al., 2004
Dlx2 C cells A cells Doetsch et al., 2002
Doublecortin (DCX) A cells Doetsch et al., 1999a; Gleeson et al., 1999
E-NCAM Neuronal-restricted precursors Chuong and Edelman, 1984
Epidermal growth factor receptor (EGFR) Activated B1 cells C cells Doetsch et al., 2002; Pastrana et al., 2009; Codega et al., 2014
GD3 Oligodendrocyte precursor cells LeVine and Goldman, 1988a, 1988b
Glial fibrillary acidic protein (GFAP) Neuroepithelial cells Radial glia B1 cells Mature astrocytes Bignami et al., 1972
Glutamate aspartate transporter (GLAST) Radial glia Shibata et al., 1997; Hartfuss et al., 2001; Doetsch, 2003; Kriegstein and Gotz, 2003
Mature astrocytes Shibata et al., 1997; Ullensvang et al., 1997
Activated B1 cells C cells Pastrana et al., 2009
ITGA6/CD49f B1 cells C cells Ramalho-Santos et al., 2002; Shen et al., 2008; Kokovay et al., 2010
LeX (CD15) B1 cells Capela and Temple, 2002
MAG Mature oligodendrocytes Quarles and Trapp, 1984
MAP2 Mature neurons Garner et al., 1988
Mash1 (Ascl1) Activated B cells Pastrana et al., 2009
C cells Parras et al., 2004; Pastrana et al., 2009
mCD24 (aka heat-stable antigen, HSA) E cells Calaora et al., 1996
A cells (transiently) Rougon et al., 1991; Nedelec et al., 1992; Calaora et al., 1996
Myelin basic protein (MBP) Mature oligodendrocytes Poduslo and Braun, 1975; Golds and Braun, 1976; Omlin et al., 1982
Nestin Neuroepithelial cells Lendahl et al., 1990
Ependymal cells Lendahl et al., 1990; Doetsch et al., 1997
Radial glia Hockfield and McKay, 1985
Activated B1 cells Codega et al., 2014
Neuronal nuclear antigen (NeuN) Mature neurons Mullen et al., 1992
Neuron-specific enolase (NSE) Mature neurons Kirino et al., 1983
NG2 Oligodendrocyte precursor cells Stallcup and Beasley, 1987; Nishiyama et al., 1996; Ong and Levine, 1999
O4 Mature oligodendrocytes Sommer and Schachner, 1981
Pax6 Cortical radial glia Gotz et al., 1998; Englund et al., 2005
Polysialylated neural cell adhesion molecule (PSA-NCAM) A cells Doetsch et al., 1997
Prominin-1 (CD133) Ependymal cells Coskun et al., 2008
Primary cilia of B1 cells Uchida et al., 2000; Marzesco et al., 2005; Pinto et al., 2008; Beckervordersandforth et al., 2010
Platelet-derived growth factor receptor α (PDGFRα) Oligodendrocyte precursor cells Hart et al., 1989; Pringle et al., 1992; Hall et al., 1996
RC1 Neuroepithelial cells Radial glia Edwards et al., 1990
RC2 Neuroepithelial cells Radial glia Misson et al., 1988; Chanas-Sacre et al., 2000; Hartfuss et al., 2001
SOX2 (SRY-Box 2) Embryonic NSCs (radial glia) Zappone et al., 2000
B1 cells Ellis et al., 2004; Ferri et al., 2004
S100-β Mature astrocytes (Not all astrocytes express it) Wang and Bordey, 2008
Ependymal cells Didier et al., 1986
Tbr1 Intermediate progenitor cells Englund et al., 2005; Hevner, 2006; Hevner et al., 2006
Tbr2 Mature neurons (cortex) Englund et al., 2005; Hevner, 2006; Hevner et al., 2006
Tuj1 (βIII Tubulin) A cells Doetsch et al., 1997; Pastrana et al., 2009
VCAM-1 Quiescent B1 cells Kokovay et al., 2012; Codega et al., 2014
Vimentin Radial glia Schnitzer and Schachner, 1981; Zecevic, 2004
Ependymal cells
Tab.1  
Fig.1  
Fig.2  
Fig.3  
Persisting Questions
• Is regional transcription factor expression controlled in the same manner throughout development and in the postnatal brain?
• Which transcription factors are permissive for multiple fates vs. instructive for a specific one?
• How is regional identity maintained postnatally?
• Is there a signaling or transcriptional threshold to induce plasticity of NSCs?
• Is there a ‘gradient of identity” or sharp cutoffs within the V-SVZ?
• How do signals within the developing V-SVZ affect specific TFs to determine the ultimate fate of an NSC?
• Can we mathematically model the input of signals experienced by NSCs that drive fate determination?
• Do SGZ NSCs have a positional identity?
• Does positional identity exist in the human brain?
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