GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway

Wang, Zongkui; Dou, Miaomiao; Liu, Fengjuan; Jiang, Peng; Ye, Shengliang; Ma, Li; Cao, Haijun; Du, Xi; Sun, Pengfei; Su, Na; Lin, Fen; Zhang, Rong; Li, Changqing

doi:10.7717/peerj.5524

Cited by 21 publications

(13 citation statements)

References 34 publications

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“…This result is consistent with data from a single-cell sequencing study which specifically profiled cells isolated from the adult mouse cerebellum [ 28 ]. Again, this is consistent with known in vitro effects of GDF11 on neurite outgrowth, dendrite formation, and synapse formation [ 29 – 31 ].…”

Section: Discussionsupporting

confidence: 89%

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

2021

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Growth differentiation factor 11 (GDF11) is a transforming factor-β superfamily member that functions as a negative regulator of neurogenesis during embryonic development. However, when recombinant GDF11 (rGDF11) is administered systemically in aged mice, it promotes neurogenesis, the opposite of its role during development. The goal of the present study was to reconcile this apparent discrepancy by performing the first detailed investigation into the expression of endogenous GDF11 in the adult brain and its effects on neurogenesis. Using quantitative histological analysis, we observed that Gdf11 is most highly expressed in adult neurogenic niches and non-neurogenic regions within the hippocampus, choroid plexus, thalamus, habenula, and cerebellum. To investigate the role of endogenous GDF11 during adult hippocampal neurogenesis, we generated a tamoxifen inducible mouse that allowed us to reduce GDF11 levels. Depletion of Gdf11 during adulthood increased proliferation of neural progenitors and decreased the number of newborn neurons in the hippocampus, suggesting that endogenous GDF11 remains a negative regulator of hippocampal neurogenesis in adult mice. These findings further support the idea that circulating systemic GDF11 and endogenously expressed GDF11 in the adult brain have different target cells or mechanisms of action. Our data describe a role for GDF11-dependent signaling in adult neurogenesis that has implications for how GDF11 may be used to treat CNS disease.

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Section: Discussionsupporting

confidence: 89%

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

2021

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“…This is consistent with prior evidence suggesting that GDF11 affects neuronal morphology and synaptic activity. Treatment of neuronal cultures with rGDF11 promotes neurite outgrowth, stimulates dendrite formation, and increases the number of excitatory synapses [26][27][28]. Interestingly, we observed the highest density of Gdf11 expression in the habenula and our results align with a recent habenula focused single-cell RNA-sequencing paper which reported Gdf11 within the top 25% of highly expressed genes in the region [29].…”

Section: Role For Gdf11 In Non-neurogenic Brain Regionssupporting

confidence: 89%

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

Mayweather

Buchanan

Rubin

2021

Preprint

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Growth differentiation factor 11 (GDF11) is a transforming factor-β superfamily member that functions as a negative regulator of neurogenesis during embryonic development. However, when recombinant GDF11 (rGDF11) is administered systemically in aged mice, it promotes neurogenesis, the opposite of its role during development. The goal of the present study was to reconcile this apparent discrepancy by performing the first detailed investigation into the expression of endogenous GDF11 in the adult brain and its effects on neurogenesis. Using quantitative histological analysis, we observed that Gdf11 is highly expressed in adult neurogenic niches and non-neurogenic regions within the hippocampus, choroid plexus, thalamus, habenula, and cerebellum. To investigate the role of endogenous GDF11 during adult hippocampal neurogenesis, we generated a tamoxifen inducible mouse that allowed us to reduce GDF11 levels. Depletion of Gdf11 during adulthood increased proliferation of neural progenitors and decreased the number of newborn neurons in the hippocampus, suggesting that endogenous GDF11 remains a negative regulator of hippocampal neurogenesis in adult mice. These findings further support the idea that circulating systemic GDF11 and endogenously expressed GDF11 in the adult brain have different target cells or mechanisms of action. Our data describe a role for GDF11-dependent signaling in adult neurogenesis that has implications for how GDF11 may be used to treat CNS disease.

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“…They added different concentrations of GDF11 to the culture medium of C17.2 neural stem cells. After 72 hours of culture, compared with the control group, different concentrations of GDF11 treatment group (12.5 ng/ml, 25 ng/ml, 50 ng/ml, 100 ng/ml) showed neural stem cell differentiation, and the high concentration of GDF11 treatment showed obvious apoptosis (the apoptosis rates of the four groups of 12.5, 25, 50, 100ng/ml were 2.1%, 9.8%, 13.1%, 17.7%, respectively) 15 . Zhang et al found that exogenous GDF11 can cause apoptosis in myocardial H9C2 cell line, whereas GDF11 knockdown reduces apoptosis 16 .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Network Analyses of Growth Differentiation Factor 11 Anti-aging Study

Zhang

Yang

Bao

2020

Preprint

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Growth differentiation factor 11 (GDF11) has been implicated in rejuvenative functions in age-related diseases. The molecular mechanisms connecting GDF11 with these anti-aging phenomena (reverse age-related cardiac hypertrophy, vascular and neurogenic rejuvenation, et al.) are still unclear. In this study, we aim to uncover the molecular functions of GDF11 using bioinformatics and network-driven analyses at human gene and transcription levels using gene co-expression network analysis and transcription factor network analysis. Our data suggests that GDF11 is involved in variety of functions such as apoptosis, DNA repair and telomere maintenance and interaction with key transcription factors such as MYC proto-oncogene (MYC), specificity protein 1 (SP1) and ETS proto oncogene 2 (ETS2). Our findings shed lights on the functions of GDF11 and provide insights into the role of GDF11 in aging.

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GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway

Cited by 21 publications

References 34 publications

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis

Bioinformatics Network Analyses of Growth Differentiation Factor 11 Anti-aging Study

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