Neonatal Subventricular Zone Neural Stem Cells Release Extracellular Vesicles that Act as a Microglial Morphogen

Subventricular zone (SVZ) neural stem cells (NSCs) are the cornerstone of the perinatal neurogenic niche. Microglia are immune cells of the nervous system that are enriched in the neonatal SVZ. Although microglia regulate NSCs, the extent to which this interaction is bi-directional is unclear. Extracellular vesicles (EVs) are cell-derived particles that encase miRNA and proteins. Here, we demonstrate that SVZ NSCs generate and release EVs. Neonatal electroporated fluorescent EV fusion proteins were released by NSCs and subsequently cleared from the SVZ. EVs were preferentially targeted to microglia. Small RNA sequencing identified miRNAs within the EVs that regulate microglia physiology and morphology. EVs induced a transition to a CD11b/Iba1 non-stellate microglial morphology. The transition accompanied a microglial transcriptional state characterized by Let-7-regulated cytokine release and a negative feedback loop that controlled NSC proliferation. These findings implicate an NSC-EV-microglia axis and provide insight to normal and pathophysiological brain development

Environmental Symbiont Acquisition May Not Be the Solution to Warming Seas for Reef-Building Corals

BACKGROUND: Coral reefs worldwide are in decline. Much of the mortality can be attributed to coral bleaching (loss of the coral's intracellular photosynthetic algal symbiont) associated with global warming. How corals will respond to increasing oceanic temperatures has been an area of extensive study and debate. Recovery after a bleaching event is dependent on regaining symbionts, but the source of repopulating symbionts is poorly understood. Possibilities include recovery from the proliferation of endogenous symbionts or recovery by uptake of exogenous stress-tolerant symbionts. METHODOLOGY/PRINCIPAL FINDINGS: To test one of these possibilities, the ability of corals to acquire exogenous symbionts, bleached colonies of Porites divaricata were exposed to symbiont types not normally found within this coral and symbiont acquisition was monitored. After three weeks exposure to exogenous symbionts, these novel symbionts were detected in some of the recovering corals, providing the first experimental evidence that scleractinian corals are capable of temporarily acquiring symbionts from the water column after bleaching. However, the acquisition was transient, indicating that the new symbioses were unstable. Only those symbiont types present before bleaching were stable upon recovery, demonstrating that recovery was from the resident in situ symbiont populations. CONCLUSIONS/SIGNIFICANCE: These findings suggest that some corals do not have the ability to adjust to climate warming by acquiring and maintaining exogenous, more stress-tolerant symbionts. This has serious ramifications for the success of coral reefs and surrounding ecosystems and suggests that unless actions are taken to reverse it, climate change will lead to decreases in biodiversity and a loss of coral reefs

Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early-Stage Ovarian Cancer

Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44+ EOC stem cells in ovarian cancer tumors and progression-free survival. EOC stem cells exist as clusters located close to the stroma forming the cancer stem cell “niche”. 17.1% of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells). In addition, the number of CD44+ EOC stem cells was significantly higher in patients with early-stage ovarian cancer (FIGO I/II), and it was associated with shorter progression-free survival (P = 0.026). This study suggests that quantification of the number of EOC stem cells in the tumor can be used as a predictor of disease and could be applied for treatment selection in early-stage ovarian cancer

Number of colonies with a given <i>Symbiodinium</i> type in each treatment detected using cp-23S-rDNA.

<p>(<b>A–D</b>) Symbiont communities (A) prior to heat-induced bleaching (PreBL), (B) after corals had lost up to 90% of their symbionts at the end of heat treatment (PostBL), (C) after three and (D) five weeks of exposure to a novel symbiont type “Other”  =  types B178, B184 and/or A194 found alone and “B170+ other”  =  B170 found alone or in conjunction with types B178, B184 and/or A194. “Other + A188”  =  type A188 found at low levels with B170+ others in 3 colonies; “B224+other”  =  types B170, B178 and B184 found in conjunction with B224. Note that B224 was also detected at low levels in 3 of 15 colonies in the D206 treatment during the 3 wks sampling (C). B224 was not detected in any other treatment or in field surveys of over 180 colonies (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013258#pone-0013258-g001" target="_blank">Fig. 1</a>). Given that the D206 tank was adjacent to the B224 treatment tank the B224 tank is the most likely source of the B224 contamination.</p

<i>Porites divaricata</i> colonies.

<p>(A) before, and (B) after one month at elevated temperature.</p

Number of colonies with a given <i>Symbiodinium</i> type in the B224 and D206 treatments detected using qPCR primers specific.

<p>qPCR primers were employed for secondary screening in the (A) B224 treatment and (B) D206 treatment. Sampling times- Pre BL; Post BL 3 wks and 5 wks as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013258#pone-0013258-g002" target="_blank">Figure 2</a> (A–D); After 14 and 28 wks: colonies from the B224 treatment were returned to the field where lower sample sizes indicate loss of colonies from storms.</p