Contributions
Abstract: P470
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Spontaneous neural repair from endogenous neural stem cells (NSCs) niches occurs in response to central nervous system (CNS) injuries to only a limited extent. Uncovering the mechanisms that control neural repair and can be further manipulated to promote NSCs towards oligodendrocyte progenitors cells (OPCs) and myelinating oligodendrocytes is a major objective.
In the current study, we describe high throughput transcriptional changes in adult mouse subventricular zone (SVZ)-NSCs during differentiation in vitro. In order to identify myelin specific transcriptional regulators amongst large transcriptional changes associated with differentiation we have focused on transcripts encoding transcription factors and regulators showing expression profile that is highly correlated with expression of myelin encoding genes. We have revealed previously undescribed effect of Prickle1 and Nfe2l3 transcriptional regulators that are positively correlated (r=0.92, p=2.8x10-10 and r=0.88, p=7.8x10-9, respectively) with expression of myelin basic protein (MBP). Using Prickle1 and Nfe2l3 silencing and immunocytochemistry approaches we demonstrated that silencing of Prickle1 dramatically decreases differentiation to NG2+OPCs by 90.6% (p< 0.002) while Nfe2l3 moderately decreases by 31.9% (p< 0.04) as compared with control siRNA. Moreover, silencing of Prickle1 also decreases maturation of OPCs to MBP+oligodendrocytes by 77.4%
(p< 0.002). This inhibitory effect of Prickle1 silencing was also evident at different time points of NSCs differentiation to NG2+OPCs and CNPase+ or MBP+oligodendrocytes.
Our findings demonstrate the role of Prickle1 in positive regulation of differentiation and maturation of oligodendrocytes suggesting that targeting Prickle1 in CNS injuries and particularly in demyelinating disease could promote generation of myelinating oligodendrocytes from endogenous niches to replenish damaged oligodendrocytes.
Disclosure:
Rina Zilkha-Falb: nothing to disclose
Michael Gurevich: nothing to disclose
Erez Hanael: nothing to disclose
Anat Achiron: nothing to disclose
Abstract: P470
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Spontaneous neural repair from endogenous neural stem cells (NSCs) niches occurs in response to central nervous system (CNS) injuries to only a limited extent. Uncovering the mechanisms that control neural repair and can be further manipulated to promote NSCs towards oligodendrocyte progenitors cells (OPCs) and myelinating oligodendrocytes is a major objective.
In the current study, we describe high throughput transcriptional changes in adult mouse subventricular zone (SVZ)-NSCs during differentiation in vitro. In order to identify myelin specific transcriptional regulators amongst large transcriptional changes associated with differentiation we have focused on transcripts encoding transcription factors and regulators showing expression profile that is highly correlated with expression of myelin encoding genes. We have revealed previously undescribed effect of Prickle1 and Nfe2l3 transcriptional regulators that are positively correlated (r=0.92, p=2.8x10-10 and r=0.88, p=7.8x10-9, respectively) with expression of myelin basic protein (MBP). Using Prickle1 and Nfe2l3 silencing and immunocytochemistry approaches we demonstrated that silencing of Prickle1 dramatically decreases differentiation to NG2+OPCs by 90.6% (p< 0.002) while Nfe2l3 moderately decreases by 31.9% (p< 0.04) as compared with control siRNA. Moreover, silencing of Prickle1 also decreases maturation of OPCs to MBP+oligodendrocytes by 77.4%
(p< 0.002). This inhibitory effect of Prickle1 silencing was also evident at different time points of NSCs differentiation to NG2+OPCs and CNPase+ or MBP+oligodendrocytes.
Our findings demonstrate the role of Prickle1 in positive regulation of differentiation and maturation of oligodendrocytes suggesting that targeting Prickle1 in CNS injuries and particularly in demyelinating disease could promote generation of myelinating oligodendrocytes from endogenous niches to replenish damaged oligodendrocytes.
Disclosure:
Rina Zilkha-Falb: nothing to disclose
Michael Gurevich: nothing to disclose
Erez Hanael: nothing to disclose
Anat Achiron: nothing to disclose