Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone
Ferrari E, Hamama L, Herrero C, Petrini C from Coronas V, Terrié E, Domenichini F, et al. (2018-2019-2020)
Introduction
Pharmacological inhibition of SOC inhibits SVZ cell proliferation
Conclusion
SVZ cells proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation in DNA. SKF-96365 and YM-58483 are both SOC inhibitors. SKF-96365 and YM-58483 dose-dependently decrease BrdU incorporation meaning that the inibition of SOC significantly reduce SVZ cell culture growth. It is important to note that this decrease of SVZ cell numbers is not related to an increase of cell death.
SVZ stem cells possess SOC that support SOCE in response to calcium store depletion. These channels control NSC self-renewal by acting on the balance of symmetric versus asymmetric stem cells divisions.
Brain injuries trigger calcium waves that activate the Neuronal Stem Cells (NSC) of the SubVentricular Zone (SVZ). Store-operated calcium entry (SOCE) allows Ca2+ influx into the cell from the extracellular space. Activated by emptying of intracellular Ca2+ stores, SOCE occcurs through Store-Operated Channel (SOC).
Perspectives
SOC may play a big part in the shift of NSC’s type of division observed during brain lesions and therefore be a starting point for future studies on their role in brain repair. Another study track suggested in the articles from the 4CS lab would be the role of SOC in the deregulation of NSC proliferation observed in glioblastomas.
More details about this experiment
More info on the SVZ
CLICK ME!
Pharmacological blockage of SOC shifts the type of SVZ stem cell division from symmetric proliferative to asymmetric
More info on SOC
SVZ Cells Possess Functional SOC
Both SKF-96365 and YM-58483 significantly diminish symmetric proliferative divisions for the benefit of asymmetric divisions. This implies that SOC inhibition decreases the NSC population by shifting the type of division from symmetric proliferative to asymmetric.
SVZ cells derived from adult mice brains were cultured as neurospheres and analyzed for the presence of TRPC1, Orai1, and STIM1 by immunostaining. The same immunostaining was also performed on mice brain sections and confirmed the presence of SOC in vivo.
Sources
All references and scientific articles used for this poster
Results of the immunostaining
More details about this experiment
Subventricular zone details :
The SVZ is the major NSC niche in the brain of adult mammals. Within this region, NSC proliferate, self-renew and give birth to neurons and glial cells. NSC are recruited by injuries and contribute to brain repair and functional recovery.
Laboratoire 4CS – Un laboratoire de l'Université de Poitiers
Coronas V, Terrié E, Déliot N, Arnault P, Constantin B. (2020) Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells. Front Cell Neurosci. 14:600018. doi: 10.3389/fncel.2020.600018. eCollection 2020. Terrié E, Coronas V, Constantin B. (2019) Role of the calcium toolkit in cancer stem cells. Cell Calcium. 2019 May 8;80:141-151. Domenichini F, Terrié E, Arnault P, Harnois T, Magaud C, Bois P, Constantin B, Coronas V. (2018) Calcium signals triggered by the microenvironment regulate neural stem cell proliferation and self-renewal in the brain subventricular zone. Stem Cells doi: 10.1002/stem.2786. https://www.researchgate.net/publication/356107942/figure/download/fig1/AS:1088823471673344@1636607153545/Schematic-representation-of-store-operated-calcium-entry-SOCE-in-ECs-Stromal.png
Atlas Thumbnails :: Allen Brain Atlas: Mouse Brain
Protocol used to determine the effect of SOC inhibitors on SVZ cells proliferation
Store-operant channels details :
SOCE is an important pathway for calcium influx from the extracellular space to the intracellular space. One of the main actors in the SOCE phenomenon are the SOC. SOC are mainly formed of Orai1 and TRPC1 (transient receptor potential canonical). SOCE is triggered after the release of calcium from the ER (endothelial reticulum) stores. This reduction is sensed by STIM1 (a sensor of calcium level in the ER). Once STIM1 is activated, it can interact with Orai1, activate SOC and thereby induce a calcium entry (called a SOCE).
Intracellular pathway of SOCE
Immunostaining of TRPC1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
Immunostaining of Orai1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
Immunostaining of STIM1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
NSC are characterized in vitro by both their capacity to give rise to neurospheres and to self-renew when cultured in the presence of mitogens. Primary neurospheres contain both stem cells (SOX2+ cells) and their progenies (SOX2- cells).
Protocol used to determine the type of division of the cells of the SVZ with or without SOC inhibitors
Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone
Célia Petrini
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Transcript
Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone
Ferrari E, Hamama L, Herrero C, Petrini C from Coronas V, Terrié E, Domenichini F, et al. (2018-2019-2020)
Introduction
Pharmacological inhibition of SOC inhibits SVZ cell proliferation
Conclusion
SVZ cells proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation in DNA. SKF-96365 and YM-58483 are both SOC inhibitors. SKF-96365 and YM-58483 dose-dependently decrease BrdU incorporation meaning that the inibition of SOC significantly reduce SVZ cell culture growth. It is important to note that this decrease of SVZ cell numbers is not related to an increase of cell death.
SVZ stem cells possess SOC that support SOCE in response to calcium store depletion. These channels control NSC self-renewal by acting on the balance of symmetric versus asymmetric stem cells divisions.
Brain injuries trigger calcium waves that activate the Neuronal Stem Cells (NSC) of the SubVentricular Zone (SVZ). Store-operated calcium entry (SOCE) allows Ca2+ influx into the cell from the extracellular space. Activated by emptying of intracellular Ca2+ stores, SOCE occcurs through Store-Operated Channel (SOC).
Perspectives
SOC may play a big part in the shift of NSC’s type of division observed during brain lesions and therefore be a starting point for future studies on their role in brain repair. Another study track suggested in the articles from the 4CS lab would be the role of SOC in the deregulation of NSC proliferation observed in glioblastomas.
More details about this experiment
More info on the SVZ
CLICK ME!
Pharmacological blockage of SOC shifts the type of SVZ stem cell division from symmetric proliferative to asymmetric
More info on SOC
SVZ Cells Possess Functional SOC
Both SKF-96365 and YM-58483 significantly diminish symmetric proliferative divisions for the benefit of asymmetric divisions. This implies that SOC inhibition decreases the NSC population by shifting the type of division from symmetric proliferative to asymmetric.
SVZ cells derived from adult mice brains were cultured as neurospheres and analyzed for the presence of TRPC1, Orai1, and STIM1 by immunostaining. The same immunostaining was also performed on mice brain sections and confirmed the presence of SOC in vivo.
Sources
All references and scientific articles used for this poster
Results of the immunostaining
More details about this experiment
Subventricular zone details :
The SVZ is the major NSC niche in the brain of adult mammals. Within this region, NSC proliferate, self-renew and give birth to neurons and glial cells. NSC are recruited by injuries and contribute to brain repair and functional recovery.
Laboratoire 4CS – Un laboratoire de l'Université de Poitiers Coronas V, Terrié E, Déliot N, Arnault P, Constantin B. (2020) Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells. Front Cell Neurosci. 14:600018. doi: 10.3389/fncel.2020.600018. eCollection 2020. Terrié E, Coronas V, Constantin B. (2019) Role of the calcium toolkit in cancer stem cells. Cell Calcium. 2019 May 8;80:141-151. Domenichini F, Terrié E, Arnault P, Harnois T, Magaud C, Bois P, Constantin B, Coronas V. (2018) Calcium signals triggered by the microenvironment regulate neural stem cell proliferation and self-renewal in the brain subventricular zone. Stem Cells doi: 10.1002/stem.2786. https://www.researchgate.net/publication/356107942/figure/download/fig1/AS:1088823471673344@1636607153545/Schematic-representation-of-store-operated-calcium-entry-SOCE-in-ECs-Stromal.png Atlas Thumbnails :: Allen Brain Atlas: Mouse Brain
Protocol used to determine the effect of SOC inhibitors on SVZ cells proliferation
Store-operant channels details :
SOCE is an important pathway for calcium influx from the extracellular space to the intracellular space. One of the main actors in the SOCE phenomenon are the SOC. SOC are mainly formed of Orai1 and TRPC1 (transient receptor potential canonical). SOCE is triggered after the release of calcium from the ER (endothelial reticulum) stores. This reduction is sensed by STIM1 (a sensor of calcium level in the ER). Once STIM1 is activated, it can interact with Orai1, activate SOC and thereby induce a calcium entry (called a SOCE).
Intracellular pathway of SOCE
Immunostaining of TRPC1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
Immunostaining of Orai1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
Immunostaining of STIM1 on SVZ cell culture (left) and mice brain section (right). Arrowheads indicate the SVZ.
NSC are characterized in vitro by both their capacity to give rise to neurospheres and to self-renew when cultured in the presence of mitogens. Primary neurospheres contain both stem cells (SOX2+ cells) and their progenies (SOX2- cells).
Protocol used to determine the type of division of the cells of the SVZ with or without SOC inhibitors