Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone. (1st February 2018)

• Record Type: Journal Article
• Authors: Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie
• Is Part Of: Stem cells. Volume 36:Number 5(2018)
• Page Start: 761
• Page End: 774
• Publication Date: 2018-02-01
• Subjects: Adult stem cells -- Calcium flux -- Nervous system -- Neural stem cell -- Self-renewal -- Stem cell asymmetry -- Stem cell–microenvironment interactions -- Stem cells -- Neurogenesis/neural regeneration -- Stem cell niche; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2786
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Abstract : Numerous signals from the microenvironment, following interaction with their receptors, can trigger a signal transduction cascade that leads to IP3 production and calcium release from the endoplasmic reticulum (ER). Stromal interaction molecule 1 senses the reduction of calcium concentration in the ER, oligomerizes and activates store-operated channels to induce a store-operated calcium entry. This calcium entry (a) allows the refilling of calcium stores via the ER calcium pump (sarco-endoplasmic reticulum calcium-ATPase SERCA) and (b) triggers a signaling cascade that promotes adult neural stem cell proliferation and self-renewal by acting on the balance of symmetric versus asymmetric division of stem cells.