Orchestrating transcriptional control of adult neurogenesis

Hsieh, Jenny

doi:10.1101/gad.187336.112

Cited by 186 publications

(171 citation statements)

References 156 publications

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“…Ribosomal biogenesis involves the synthesis of the machinery involved in polypeptide formation, and subsequently determines the translational capacity of a cell (Bernstein, Gallagher, Mitchell, Granneman, & Baserga, 2004). Our findings corroborate previous studies implicating increases in ribosomal biogenesis in cells undergoing increases in proliferation, neurite formation and synaptogenesis (Hsieh, 2012). …”

Section: Discussionsupporting

confidence: 93%

The genome‐wide expression effects of escitalopram and its relationship to neurogenesis, hippocampal volume, and antidepressant response

Powell

Murphy

Jong

et al. 2017

American J of Med Genetics Pt B

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Antidepressant‐induced hippocampal neurogenesis (AHN) is hypothesized to contribute to increases in hippocampal volume among major depressive disorder patients after long‐term treatment. Furthermore, rodent studies suggest AHN may be the cellular mechanism mediating the therapeutic benefits of antidepressants. Here, we perform the first investigation of genome‐wide expression changes associated with AHN in human cells. We identify gene expression networks significantly activated during AHN, and we perform gene set analyses to probe the molecular relationship between AHN, hippocampal volume, and antidepressant response. The latter were achieved using genome‐wide association summary data collected from 30,717 individuals as part of the ENIGMA Consortium (genetic predictors of hippocampal volume dataset), and data collected from 1,222 major depressed patients as part of the NEWMEDS Project (genetic predictors of response to antidepressants dataset). Our results showed that the selective serotonin reuptake inhibitor, escitalopram evoked AHN in human cells; dose‐dependently increasing the differentiation of cells into neuroblasts, as well as increasing gliogenesis. Activated genome‐wide expression networks relate to axon and microtubule formation, and ribosomal biogenesis. Gene set analysis revealed that gene expression changes associated with AHN were nominally enriched for genes predictive of hippocampal volume, but not for genes predictive of therapeutic response.

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Section: Discussionsupporting

confidence: 93%

The genome‐wide expression effects of escitalopram and its relationship to neurogenesis, hippocampal volume, and antidepressant response

Powell

Murphy

Jong

et al. 2017

American J of Med Genetics Pt B

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“…Defects in neuroblast lineage progression cause abnormal neural circuits and neurological disorders (Ming and Song, 2011;Zhao et al, 2008). Despite recent progress in understanding the transcriptional control of neurogenesis (Hsieh, 2012), the full inventory of transcription factors (TFs) and regulatory networks underlying neuroblast development remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression

Feng

Yang

et al. 2013

Development

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SUMMARYNeuroblasts generate neurons with different functions by asymmetric cell division, cell cycle exit and differentiation. The underlying transcriptional regulatory pathways remain elusive. Here, we performed genetic screens in C. elegans and identified three evolutionarily conserved transcription factors (TFs) essential for Q neuroblast lineage progression. Through live cell imaging and genetic analysis, we showed that the storkhead TF HAM-1 regulates spindle positioning and myosin polarization during asymmetric cell division and that the PAR-1-like kinase PIG-1 is a transcriptional regulatory target of HAM-1. The TEAD TF EGL-44, in a physical association with the zinc-finger TF EGL-46, instructs cell cycle exit after the terminal division. Finally, the Sox domain TF EGL-13 is necessary and sufficient to establish the correct neuronal fate. Genetic analysis further demonstrated that HAM-1, EGL-44/EGL-46 and EGL-13 form three transcriptional regulatory pathways. We have thus identified TFs that function at distinct developmental stages to ensure appropriate neuroblast lineage progression and suggest that their vertebrate homologs might similarly regulate neural development.

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“…Although progress has been made in identifying transcription factors (TFs) that regulate different steps of neurogenesis in the postnatal and adult brain (Hsieh 2012), the nature of the factors that mediate the activity of extrinsic signals and determine cell-intrinsically the quiescent or proliferating state of NSCs is still largely unknown. Elucidating these transcriptional mechanisms is essential to understand how the physiology and behavior of NSCs is regulated and, in the longer term, develop therapeutic interventions; e.g., to counteract the decline of neurogenesis in the aging brain.…”

mentioning

confidence: 99%

Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

Martynoga¹,

et al. 2013

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The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, the transcriptional mechanisms involved are mostly unknown, largely due to lack of a cell culture model. In this study, we first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular and transcriptional characteristics of quiescent cells. We then use epigenomic profiling to identify enhancers associated with the quiescent NS cell state. Motif enrichment analysis of these enhancers predicts a major role for the nuclear factor one (NFI) family in the gene regulatory network controlling NS cell quiescence. Interestingly, we found that the family member NFIX is robustly induced when NS cells enter quiescence. Using genome-wide location analysis and overexpression and silencing experiments, we demonstrate that NFIX has a major role in the induction of quiescence in cultured NSCs. Transcript profiling of NS cells overexpressing or silenced for Nfix and the phenotypic analysis of the hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by regulating the interactions of NSCs with their microenvironment.

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Orchestrating transcriptional control of adult neurogenesis

Cited by 186 publications

References 156 publications

The genome‐wide expression effects of escitalopram and its relationship to neurogenesis, hippocampal volume, and antidepressant response

The genome‐wide expression effects of escitalopram and its relationship to neurogenesis, hippocampal volume, and antidepressant response

Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression

Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

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