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Glendinning, M. D.

Publications and source records attributed to Glendinning, M. D..

2 recordsLinked to original sources

miR-126 modulates neural progenitor cell development

Noncoding microRNAs (miRNAs) play important roles in controlling signaling pathways by targeting multiple genes and altering their expression levels. MiR-126 is a known endothelial-specific miRNA that regulates vascular integrity and angiogenesis by enhancing proangiogenic actions of VEGF and FGF. MiR-126 is also expressed in several stem cell compartments, including embryonic stem cell (ESC) and hematopoietic stem/progenitor cells (HSPC) where it regulates cell differentiation and quiescence. Here we show that miR-126 is expressed as well in neural progenitor cells where it regulates cell differentiation by targeting genes of the IGF1R signaling pathway including IRS1, PI3K and AKT. Moreover, Hoxa9 and IGF-1 expression by neural progenitor cells is upregulated when miR-126 expression levels are reduced. Our data, implicating a role for miR-126 in manipulating cell development, could open a window of opportunities for clinical purposes and therapeutic strategies to achieve controlling neural progenitor cell behavior. HighlightsO_LIKnockdown of miR-126 in neural progenitor cells increases cell proliferation C_LIO_LImiR-126 modulates expression levels of HoxA9 and known target genes involved in the IGF1R signaling pathway in neural progenitor cells C_LIO_LIOverexpression of miR-126 results in induced cell differentiation in neural progenitor cells C_LIO_LImiR-126 affects motor neuron development in the thoracic region of the spinal cord C_LIO_LIKnockdown of miR-126 expression results in increased IGF-1 expression C_LI

cell biology↗

Single-cell RNA sequencing implicates venous endothelial cells as a source of VEGF-mediated neo-angiogenesis in neuroinflammation

Histopathological studies of multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), and its animal model, experimental autoimmune encephalomyelitis (EAE), have found newly formed leaky vessels in demyelinated acute and chronic plaques, in addition to blood-brain barrier (BBB) damage in existing vessels, that exacerbate disease pathology by increasing infiltration of immune cells. Which vessel subtypes and signaling pathways generate these aberrant vessels is poorly understood. Using single-cell RNA-sequencing and in vivo validation, we find that transcriptome signatures of neo-angiogenesis arise in venous endothelial cells in both acute and chronic EAE, and correlate with upregulation in VEGF-A signaling. These neo-angiogenic markers are also increased in acute and chronic MS lesions. Treatment with a VEGF-A blocking antibody diminishes neo-angiogenic transcriptomic signatures and vascular proliferation in vivo, but does not restore BBB function or ameliorate significantly EAE pathology. Therefore, anti-angiogenic therapies in combination with immunomodulatory therapies may benefit MS progression.

neuroscience↗