REST Regulates Non–Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II Article Swipe
Hyung Joon Kim
,
Ahmet M. Denli
,
Rebecca A. Wright
,
Tithi D. Baul
,
Gregory D. Clemenson
,
Ari S. Morcos
,
Chunmei Zhao
,
Simon T. Schafer
,
Fred H. Gage
,
Mohamedi N. Kagalwala
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1523/jneurosci.4286-14.2015
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1523/jneurosci.4286-14.2015
RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non–cell-autonomous role. Gene expression analysis identified Secretogranin II ( Scg2 ) as the major secreted REST target responsible for the non–cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro , and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo . In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non–cell-autonomously via SCG2. SIGNIFICANCE STATEMENT Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell-intrinsic and non–cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo , REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1523/jneurosci.4286-14.2015
- https://www.jneurosci.org/content/jneuro/35/44/14872.full.pdf
- OA Status
- bronze
- Cited By
- 44
- References
- 31
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2130842203
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2130842203Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1523/jneurosci.4286-14.2015Digital Object Identifier
- Title
-
REST Regulates Non–Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin IIWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2015Year of publication
- Publication date
-
2015-11-04Full publication date if available
- Authors
-
Hyung Joon Kim, Ahmet M. Denli, Rebecca A. Wright, Tithi D. Baul, Gregory D. Clemenson, Ari S. Morcos, Chunmei Zhao, Simon T. Schafer, Fred H. Gage, Mohamedi N. KagalwalaList of authors in order
- Landing page
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https://doi.org/10.1523/jneurosci.4286-14.2015Publisher landing page
- PDF URL
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https://www.jneurosci.org/content/jneuro/35/44/14872.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://www.jneurosci.org/content/jneuro/35/44/14872.full.pdfDirect OA link when available
- Concepts
-
Rest (music), Progenitor cell, Neural stem cell, Cell biology, Progenitor, Neuroscience, Biology, Stem cell, Physics, AcousticsTop concepts (fields/topics) attached by OpenAlex
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44Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 4, 2023: 5, 2022: 3, 2021: 8Per-year citation counts (last 5 years)
- References (count)
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31Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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