NICD-mediated notch transduction regulates the different fate of chicken primordial germ cells and spermatogonial stem cells

Abstract

BackgroundNotch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated.ResultsIn our studies, Overexpression of the Notch1 NICD promoted development of the reproductive ridge, but inhibited the formation of seminiferous tubules. The formation efficiency of PGCs in the reproductive ridge following overexpression of NICD (7.5% ± 0.11) was significantly higher than that (4.9% ± 0.17, p < 0.05) following inhibition of NICD, While the formation efficiency of spermatogonial stem cells (SSCs) in the testes (12.7% ± 0.08) was significantly lower after NICD overexpression than that after inhibition of NICD (16.3% ± 0.16, p < 0.05). Using co-immunoprecipitation, we found that this anomaly stemmed from the reversal of dissociation of the Notch-regulated transcription factor CBF-1/RBP co-suppression complex during the differentiation of PGCs into SSCs. This dissociation of the CBF-1/RBP co-suppressing complex during the differentiation of ESCs into PGCs resulted in the release of HDAC1 and HDAC2 and the recruitment of mastermind-like 1 to form a coactive complex to promote the expression of the downstream transcription suppressor hairy/enhancer of split-1. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes.ConclusionsIn summary, Notch signaling plays diametrically opposing roles during normal development of chicken PGCs and SSCs, and these functions was determined by the expression of NICD, changes in the CBF-1/RBP complex composition, and histone modification.Electronic supplementary materialThe online version of this article (10.1186/s13578-018-0238-y) contains supplementary material, which is available to authorized users.

Microarray meta‐analysis identifies candidate genes for human spermatogenic arrest

“…HDAC2, which regulates gene expression (Ashburner, Westerheide, & Baldwin, ), is essential for self‐renewal and maintenance of spermatogonial stem cells (SSCs; Kofman, Huszar, & Payne, ), and low HDAC2 expression leads to activation of the p53/p21 pathway (Li et al, ). This expression inhibition of HDAC2 in our results may be associated with activation of the notch signalling pathway, which was overrepresented in our results, and HDAC2 expression showed dramatic alterations during the differentiation of primordial germ cells (PGCs) into SSCs (Zuo et al, ). Nevertheless, genes regulated by HDAC2 during spermatogenesis require further exploration to determine the relationship between HDAC2 and spermatogenic failure.…”

C1EIP Functions as an Activator of ENO1 to Promote Chicken PGCs Formation via Inhibition of the Notch Signaling Pathway

“…Further analysis of the protein interaction network with PCViz and GeneMANIA database revealed the direct regulatory relationship between ENO1 and Myc as well as Myc and Notch1 ( Figure 5C ). Myc and Notch1 are important signaling molecules in the Notch signaling pathway, which is a crucial pathway associated with the formation of PGCs ( Zuo et al, 2018b ). C1EIP and ENO1 might affect PGC formation through the Notch signaling pathway.…”

“…Recently, we identified multiple genes and pathways involved in germ cell differentiation and systematically described the role of these pathways and gene function in this process, including BMP4, TGF-BETA, JAK/STAT, Wnt, MAPK, and PPAR ( Zhang L. et al, 2015 ; Zhang et al, 2016 ; Cheng et al, 2018 ; He et al, 2018 ; Zuo et al, 2018b ). A new PGC-specific gene, C2EIP (Chromosome 2 Expression in PGCs), which may direct chicken PGC formation via HH (Hedgehog) signaling, has been identified ( Zuo et al, 2016 , 2018a ).…”

Neonatal Anesthesia by Ketamine in Rats Interferes with Proliferation and Differentiation of Hippocampal Neural Stem Cells and Neurocognitive Function in Adulthood via Inhibition of Notch1 Signalling Pathway

“…In the present study, Jagged1 and LV-NICD1 were microinjected into the bilateral hippocampal DG. Jagged1 can activate Notch1 signalling through extracellular pathway [38] and overexpression of NICD1 can activate Notch1 signalling through intracellular pathway [39] . Therefore, we choose two methods (Jagged1 or LV-NICD1) to activate Notch1 signalling through extracellular and intracellular pathway respectively.…”