Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

García-Gutiérrez, Pablo; Juárez-Vicente, Francisco; Wolgemuth, Debra J.; García‐Domínguez, Mario

doi:10.1242/jcs.147462

Cited by 37 publications

(24 citation statements)

References 58 publications

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“…CD11c + microglia may contribute to shaping axonal organization in the CNS through expression of well‐described axonal guidance signals such as Cxcl12, Ntn1, Plxna2 , and Sema7a . They may stimulate neuronal and neurite outgrowth and astrocytogenesis through expression of Ptn (Garcia‐Gutierrez et al , ), Gpx3 (Buchser et al , ), and Bmp2 (Nakashima et al , ), respectively, and affect remodeling processes in the developing brain tissue by expression of metalloproteinases Mmp12, Mmp19 , and Mmp24 . CD11c + microglia are therefore seen to be involved in promoting and directing organization of the developing CNS.…”

Section: Discussionmentioning

confidence: 99%

A novel microglial subset plays a key role in myelinogenesis in developing brain

et al. 2017

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Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation‐activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c+ microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin‐like growth factor 1, and its selective depletion from CD11c+ microglia leads to impairment of primary myelination. CD11c‐targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c+ microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis.

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Section: Discussionmentioning

confidence: 99%

A novel microglial subset plays a key role in myelinogenesis in developing brain

et al. 2017

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“…Cells were transfected either with empty or with E protein expression vector, and were cultured in proliferation medium (with EGF and FGF). Transcript levels of proneural genes pleotrophin (PTN), SPOCK1, doublecortin (DCX), and ROBO2 were analyzed in fNSCs 24 h post transfection [47][48][49][50][51]. Robust increase in mRNA levels of these pro-neural genes was observed in response to E protein.…”

Section: Zv E Protein Alters Cell Cycle Dynamics Of Fnscs and Inducesmentioning

confidence: 99%

Zika virus E protein alters the properties of human fetal neural stem cells by modulating microRNA circuitry

et al. 2018

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Zika virus (ZV) infects neural stem cells (NSCs) and causes quiescence in NSCs, reducing the pool of brain cells, leading to microcephaly. Despite conscientious efforts, the molecular mechanisms for ZV-mediated effects on NSCs lack clarity. This study aimed to explore the underlying mechanisms for ZV-mediated induction of quiescence in the primary cultures of human fetal neural stem cells (fNSCs). We demonstrate that expression of ZV envelope (E) protein displays maximum quiescence in human fNSCs by accumulating cells in the G0/G1 phase of the cell cycle as compared to other non-structural proteins, viz. NS2A, NS4A and NS4B. E protein induces immature differentiation by induction of pro-neuronal genes in proliferating fNSCs, induces apoptosis in differentiating fNSCs 3 days post differentiation, and disrupts migration of cells from differentiating neurospheres. In utero electroporation of mouse brain with E protein shows drastic downregulation of proliferating cells in ventricular and subventricular zone regions. Global microRNA sequencing suggests that E protein modulates miRNA circuitry. Among differentially expressed miRNAs, we found 14 upregulated and 11 downregulated miRNAs. Mir-204-3p and mir-1273g-3p directly regulate NOTCH2 and PAX3 expression, respectively, by binding to their 3'UTR. Bioinformatic analysis using GO analysis for the targets of differentially expressed miRNAs revealed enrichment of cell cycle and developmental processes. Furthermore, WNT, CCKR, PDGF, EGF, p53, and NOTCH signaling pathways were among the top enriched pathways. Thus, our study provides evidence for the involvement of ZV E protein and novel insights into the molecular mechanism through identification of miRNA circuitry. Art work depicting the effect of Zika virus E protein on human fetal neural stem cells.

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“…Pleiotropin (Ptn), also known as heparin-binding growth-associated molecule (HB-GAM) and osteoblast-specific factor 1 (Osf1), is a secreted multifunctional cytokine and involved in regulating the proliferation of various cell types and inducing the differentiation of neural stem cells, oligodendrocyte precursor cells, P19 cells, bone marrow cells, and mesenchymal stem cells (Bouderlique et al, 2014;Garcia-Gutierrez, Juarez-Vicente, Wolgemuth, & Garcia-Dominguez, 2014;Hienola, Pekkanen, Raulo, Vanttola, & Rauvala, 2004;Himburg et al, 2010;Kuboyama, Fujikawa, Suzuki, & Noda, 2015;Miao et al, 2012;S. Yang et al, 2013;X.…”

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confidence: 99%

Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone

Tao

Yang

et al. 2017

Journal Cellular Physiology

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Ptn is a pleiotropic growth factor involving in the regulation of cellular proliferation and differentiation, but its biological function in uterine decidualization remains unknown. Here, we showed that Ptn was highly expressed in the decidual cells, and could induce the proliferation of uterine stromal cells and expression of Prl8a2 and Prl3c1 which were two well-established differentiation markers for decidualization, suggesting an important role of Ptn in decidualization. In the uterine stromal cells, progesterone stimulated the expression of Ptn accompanied with an accumulation of intracellular cAMP level. Silencing of Ptn impeded the induction of progesterone and cAMP on the differentiation of uterine stromal cells. Administration of PKA inhibitor H89 resulted in a blockage of progesterone on Ptn expression. Further analysis evidenced that regulation of progesterone and cAMP on Ptn was mediated by C/EBPβ. During in vitro decidualization, knockdown of Ptn could weaken the up-regulation of Prl8a2 and Prl3c1 elicited by C/EBPβ overexpression, while constitutive activation of Ptn reversed the repressive effects of C/EBPβ siRNA on the expression of Prl8a2 and Prl3c1. Meanwhile, Ptn might mediate the regulation of C/EBPβ on Hand2 which was a downstream target of Ptn in the differentiation of uterine stromal cells. Attenuation of Ptn or C/EBPβ by specific siRNA blocked the stimulation of Hand2 by progesterone and cAMP. Collectively, Ptn may play a vital role in the progesterone-induced decidualization pathway.

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Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

Cited by 37 publications

References 58 publications

A novel microglial subset plays a key role in myelinogenesis in developing brain

A novel microglial subset plays a key role in myelinogenesis in developing brain

Zika virus E protein alters the properties of human fetal neural stem cells by modulating microRNA circuitry

Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone

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