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Aging-US: PirB functions as an intrinsic suppressor in hippocampal neural stem cells


Aging-US published "PirB functions as an intrinsic suppressor in hippocampal neural stem cells" which reported that neural stem cells play pivotal roles during prenatal development and throughout life.

PirB expression increased with age during development, and its deficiency promoted neural stem cell proliferation and differentiation in vivo and in vitro.

Furthermore, the authors detected an increase in Type 1 neural stem cells in PirB-deficient mice compared to their wild-type littermates.

PirB deficiency promoted stemness marker gene expression of Sox2 and KLF4 by activating Akt1 phosphorylation.

These Aging-US findings suggest that PirB inhibits the self-renewal and differentiation capacities of neural stem cells.

These Aging-US findings suggest that PirB inhibits the self-renewal and differentiation capacities of neural stem cells.

Dr. Cuiping Yang and Dr. Yongbin Chen both from The Kunming Institute of Zoology said, "Neural stem cells (NSCs) generate all major neural cell types in the central nervous system (CNS), including neurons, astrocytes, and oligodendrocytes."

NSCs are radial glia-like cells with an elaborate tree of processes in the granule cell layer and GFAP expression.

Adult neurogenesis is regulated by physiological and pathological activities at all levels, which includes adult NSCs proliferation, maturation, survival, differentiation, and integration of newborn neurons.

CNS resident cells, including peripheral immune cells, participate in functional regulation during hippocampal adult neurogenesis, and the inflammatory environment enhances NSC proliferation in the SGZ.

Figure 4. PirB depletion increases the NSC pool in vivo through Akt1 signaling. (AB) Neural stem/progenitor cell (GFP-expressing cell) number quantified in the dentate gyrus of mice over time. n ≥ 3. (CD) Type 1 cells (arrows) were increased in PirB-depleted mice compared with the wild-type control group; n ≥ 3. (EF) PirB knockout increased Type 1 early progenitors in 2-month-old mice. (Green: GFP-positive; red: GFAP positive); n ≥ 3. (G) qRT-PCR relative mRNA expression of KLF4, SOX2, c-MYC, and Nestin. (H) Increases in stemness marker genes KLF4 and Sox2 were verified by western blot. (I) Akt1 phosphorylation was increased upon PirB depletion as shown by western blot. (J) Working model for PirB in NSCs. PirB deficiency promotes Akt1 phosphorylation through reducing recruitment and binding of Src homology 2-containing protein tyrosine phosphatase (SHP)-1 and SHP-2 to inactivate TrkB. This results in constitutive activation of the Akt1 signaling pathway and increased NSC self-renewal. Means ± SEM, *P < 0.05; **P < 0.01; ***P < 0.001 by the t-test.

Paired immunoglobulin-like receptors, also known as leukocyte immunoglobulin-like receptors or Ig-like transcripts in humans, are expressed on B cells and myeloid lineage cells, and include the inhibitory PirB and activating isoform PirA, which bind to class I MHC molecules.

Thus, although PirB is involved in neural development, whether intrinsic PirB can regulate the stemness maintenance of NSCs is unknown.

The Yang/Chen Research Team concluded in their Aging-US Research Paper, "our results suggest that selectively blocking PirB might be a promising therapeutic strategy for elderly or other neurodegenerative patients in the future"

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Correspondence to: Cuiping Yang email: and Yongbin Chen email:

Keywords: paired immunoglobulin-like receptor B, PirB, Akt1, neural stem cells, NSCs, neurogenesis

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

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