ライフサイエンスコーパス: proneural

1 btype (i.e., classical, mesenchymal, neural, proneural).

2 of GBMs (classical, mesenchymal, neural, and proneural).

3 erally be classified as either antineural or proneural.

4 nificant clusters of binding motifs for both proneural activator (P) proteins and basic helix-loop-he

5 transcription in cultured cells and Neurog2 proneural activities in vivo.

6 nt ATH factors displayed different levels of proneural activity as reflected by the number and functi

7 We found that Neurog2 proneural activity declines in late corticogenesis, corr

8 in2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex

9 uces neurogenesis, and SCP1 counteracts this proneural activity of miR-124.

10 Ascl1(KINgn2) transgenic mutants, where the proneural activity of Ngn2 replaces Ascl1, demonstrating

11 idue results in a form of Sc with heightened proneural activity that can rescue the loss of bristles

12 CR cell neurogenesis by tempering Neurog2's proneural activity.

13 mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma.

14 biomarker of mesenchymal GBM versus neural, proneural and classical subtypes.

15 cursors expressing different combinations of proneural and Foxn4 transcription factors.

16 osette progenitors, accompanied by increased proneural and lineage-specific transcription factor expr

17 lls (GSCs) from oligodendroglioma as well as proneural and mesenchymal glioblastoma, relative to olig

18 EV-borne protein cargos transferred between proneural and mesenchymal GSC increased protumorigenic b

19 Given that glioblastomas contain both proneural and mesenchymal GSCs, combined EZH2 and BMI1 t

20 We also identified a subclass of proneural and neural glioblastoma with significantly bet

21 hippocampal NPCs impaired the activation of proneural and neurogenic genes, resulting in increased n

22 l differentiation by promoting expression of proneural and neurogenic genes.

23 Co-knockdown of Tp53 rescues the decrease in proneural and neuronal marker expression, which is thus

24 sequential and coordinated expression of the proneural and neuronal subtype-specific genes identifies

25 , we identify a subset of tumors within the "proneural" and "classical" subtypes that are addicted to

26 um into four subtypes: classic, mesenchymal, proneural, and neural GBM.

27 The mechanisms by which proneural basic helix-loop-helix (bHLH) factors control

28 eurogenesis depends upon the function of the proneural basic helix-loop-helix (bHLH) transcription fa

29 ulture model, we find that expression of the proneural basic helix-loop-helix (bHLH) transcription fa

30 Proneural basic helix-loop-helix (bHLH) transcription fa

31 The proneural basic helix-loop-helix (bHLH) transcriptional

32 Cell intrinsic factors such as the proneural basic helix-loop-helix and homeodomain transcr

33 Proneural basic helix-loop-helix proteins are key regula

34 d transcription factor Pointed (Pnt) and the proneural basic helix-loop-helix proteins Atonal (Ato) a

35 Recent studies demonstrate that the proneural basic helix-loop-helix transcription factor Ma

36 Proneural basic helix-loop-helix transcription factor, A

37 The proneural basic helix-loop-helix transcription factors N

38 f the alpha(1B)-adrenergic receptor subtype, proneural basic helix-loop-helix transcription factors,

39 conserved patterning molecules, such as the proneural basic helix-loop-helix transcription factors.

40 sion of ID1 and ID3, decreased levels of the proneural basic HLH (bHLH) transcriptional regulators TC

41 The proneural, basic helix-loop-helix transcription factor A

42 We now report that the proneural bHLH (basic helix-loop-helix) transcription fa

43 e containing binding sites for the Su(H) and proneural bHLH A proteins.

44 ce factor Sox2, it does cause suppression of proneural bHLH gene expression, indicating that PRC2 is

45 The authors investigated the role of proneural bHLH gene neurogenin1 (ngn1) in photoreceptor

46 ed from those of other transiently expressed proneural bHLH genes, such as ash1, ath3, ath5, and ngn2

47 of proneural ectoderm independently from the proneural bHLH genes.

48 We propose that mutual inhibition between proneural bHLH proteins and Yap is an important regulato

49 Conversely, overexpression of Yap prevents proneural bHLH proteins from initiating cell cycle exit.

50 These genes encode the proneural bHLH proteins NGN-1 and HLH-2 and the Otx home

51 ion of Notch signaling revealed a cascade of proneural bHLH transcription factor gene expression that

52 , we evaluate the expression and function of proneural bHLH transcription factors during the onset of

53 X2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA

54 just before delamination and selection of a proneural cell fate in the early Drosophila embryo.

55 fore the appearance of the complete group of proneural cells.

56 Proneural class GBM had significantly lower levels of co

57 echanism whereby the regulated function of a proneural-class gene in a single neural lineage can both

58 at the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, wh

59 mours with hallmark characteristics of human proneural/classical glioblastoma.

60 Downregulation of Drosophila A2BP1 in the proneural cluster increases adult sensory bristle number

61 rential Notch signaling between cells of the proneural cluster orchestrates sensory organ specificati

62 mediate activation by proneural factors in "proneural cluster" territories, whereas R sites mediate

63 - the absence of neuroblast segregation and proneural clusters - might be used to support or reject

64 that the selection of neural precursors from proneural clusters as well as the segregation of neural

65 of m8 transcription in specific cells within proneural clusters by Notch signaling is programmed by a

66 have the opposite cell expression pattern in proneural clusters during Notch signaling.

67 anogaster, neuroblasts are not selected from proneural clusters in the branchiopod.

68 Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DR

69 In the proneural clusters that give rise to Drosophila mechanos

70 re initially expressed in clusters of cells (proneural clusters) in the neuroepithelium but expressio

71 ls do not express achaete scute homologue in proneural clusters, but express collier, a marker for po

72 ll expression pattern opposite that of m8 in proneural clusters.

73 such as Ato itself and Senseless within the proneural clusters.

74 This defines regions of proneural ectoderm independently from the proneural bHLH

75 mal EV signatures or mesenchymal tumors with proneural EV signatures were both associated with worse

76 Proneural expression of Mad-RNA interference (RNAi) or a

77 radiation induced a marked shift away from a proneural expression pattern toward a mesenchymal one.

78 ll behaviours with dynamic quantification of proneural expression to uncover the construction of the

79 lia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also kn

80 The proneural factor Ascl1 controls multiple steps of neurog

81 artially overlaps with the expression of the proneural factor Ascl1.

82 ineates the importance of choosing the right proneural factor in neuronal reprogramming strategies.

83 controlled transcriptionally by Ascl1, this proneural factor is itself required in radial glial prog

84 Of particular interest is the bHLH proneural factor Neurogenin2 (Ngn2), which orchestrates

85 Here, we show that another proneural factor, Ascl1, promotes neuronal migration in

86 It has been postulated that a proneural factor, neurogenin 1 (Ngn1), simultaneously ac

87 ubtype defined by low expression of ASCL1, a proneural factor.

88 orm ectopic neurons when supplemented with a proneural factor.

89 ng in Neuron, Pacary et al. demonstrate that proneural factors activate atypical Rho GTPases Rnd2 and

90 Previous work has shown that proneural factors also confer a migratory behaviour to c

91 precursor (SOP) fate is the synergy between proneural factors and their coactivator Senseless in tra

92 cl1 and Neurog basic helix-loop-helix (bHLH) proneural factors are expressed in a mosaic pattern in p

93 we propose a model for how the Ato and Sens proneural factors are integrated with an abdominal Hox f

94 sites in these modules mediate activation by proneural factors in "proneural cluster" territories, wh

95 The proneural factors Lethal of scute and Asense differentia

96 The proneural factors Mash1 (Ascl1) and neurogenin 2 (Ngn2)

97 gest that the mosaic expression of Foxn4 and proneural factors may serve as the trigger to initiate a

98 A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive

99 uent (and typically transient) expression of proneural factors promotes cell cycle exit, subtype spec

100 in ESNs, is activated downstream of all the proneural factors we tested, suggesting that these genes

101 tem cells, we found that two main vertebrate proneural factors, Ascl1 and neurogenin 2 (Neurog2), ind

102 sions and neurite outgrowth, we propose that proneural factors, through spatiotemporal regulation of

103 in the anterior ectoderm, consistent with a proneural function for CapI-ash1.

104 re key regulators of neurogenesis but their 'proneural' function is not well understood, partly becau

105 itor cells but also sustained expression and proneural functions in the formation of oligodendrocytes

106 3K isoform as a unique therapeutic target in proneural GBM and suggest that pharmacological mTOR inhi

107 receptor (CSF-1R) to target TAMs in a mouse proneural GBM model, which significantly increased survi

108 In proneural GBM, apelin levels were downregulated by VEGFA

109 prises several molecular subtypes, including proneural GBM.

110 ated with enhanced survival in patients with proneural GBM.

111 gistically improved survival of mice bearing proneural GBM.

112 n Dichaete, to the spatial regulation of the proneural gene achaete (ac) in the embryonic CNS.

113 also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the bir

114 as illustrated by reduced expression of the proneural gene Ascl1 (Mash1) and increased expression of

115 The proneural gene atonal (ato) encodes a basic-HLH protein

116 The activation of the proneural gene atonal (ato) in the Drosophila eye disc e

117 from within a group of cells expressing the proneural gene atonal (ato).

118 BP are required for repression of genes of a proneural gene cluster, achaete-scute complex (AS-C), in

119 The model reproduces the full time course of proneural gene expression and accounts for specific feat

120 ages have already segregated at the onset of proneural gene expression and are committed to a given f

121 f the Drosophila brain, a travelling wave of proneural gene expression initiates neurogenesis in the

122 A wave of proneural gene expression is thought to regulate the tim

123 mpetence in the Xenopus retina by activating proneural gene expression.

124 eptor (EGFR) signalling interacting with the proneural gene l'sc.

125 RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by

126 The proneural gene Math1 is known to be involved in numerous

127 essor Hes1 and preferential elevation of the proneural gene Math5.

128 The proneural gene Neurog2 is expressed in progenitors throu

129 rmediate progenitors, Sox4 partners with the proneural gene Neurogenin2 to activate Tbrain2 and then

130 developed new Flippase (FLP) reagents using proneural gene promoters to drive FLP expression very ea

131 on of Xath5 gene expression is comparable to proneural gene regulation in Drosophila, whereby separat

132 neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these e

133 ne (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differen

134 The atonal (ato) proneural gene specifies a stereotypic number of sensory

135 The atonal (ato) proneural gene specifies different numbers of sensory or

136 s show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of t

137 ctin) promoter induces the expression of the proneural gene, Neurogenin1 (Ngn1); however, the express

138 , but not in the broad pattern expected of a proneural gene.

139 activity of transcription factors encoded by proneural genes (PNGs).

140 nds to bivalently marked promoters of poised proneural genes [neurogenin 2 (Ngn2) and neurogenic diff

141 h the temporal and spatial expression of the proneural genes achaete (ac) and scute (sc).

142 ned via spatially discrete expression of the proneural genes achaete-scute (ac-sc).

143 ot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypotha

144 Here we asked whether these proneural genes also regulate laminar fate transitions.

145 NA interference that, similar to Drosophila, proneural genes are responsible for the formation and su

146 During eye development, activation of proneural genes at a moving front adds new columns to a

147 Proneural genes encode transcriptional activators of the

148 Expression analysis reveals that proneural genes for hair cells and neurons overlap withi

149 e, we demonstrate an additional function for proneural genes in the coordinated invagination and migr

150 ansgenic embryos mis-expressing any of these proneural genes in the epidermis produced ectopic midlin

151 Here we show that in mouse, the proneural genes Neurog1 and Neurog2 are coexpressed in t

152 in the embryonic cerebral cortex, where the proneural genes Neurog2 and Ascl1 are key cell fate dete

153 The proneural genes Neurog2 and Ascl1 cooperate in progenito

154 The expression of the proneural genes NeuroM and NeuroD reflects the sequence

155 ivity, but rather is regulated downstream of proneural genes that are widely expressed by neural prog

156 Proneural genes thus act in a context-dependent fashion

157 neural induction, whereas expression of the proneural genes was down-regulated, VGLUT2, GluR2, and G

158 ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral

159 s linked to the regulation of Hes1 and other proneural genes, as demonstrated by genome-wide RNA-seq

160 Proneural genes, including Achate-scute-like 1 (Ascl1) a

161 Proneural genes, including Pax6 and Neurogenin-1 and -2,

162 aling can be inhibitory to the expression of proneural genes, it is also required for interneuron for

163 scription repressor and downstream target of proneural genes, suppresses Olig2 expression and therefo

164 pecies to study the evolution of a family of proneural genes, the achaete-scute genes, and to examine

165 t Lfng acts in a feedback loop downstream of proneural genes, which, by promoting Notch activation, m

166 rgets MASH1 and NGN1, two well-characterized proneural genes.

167 t and neuronal fates by controlling specific proneural genes.

168 cells depends on the accurate expression of proneural genes.

169 enes, and the closest homologue to ancestral proneural genes.

170 tex, we found that RAS/ERK signals control a proneural genetic switch, inhibiting Neurog2 expression

171 s inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated th

172 ing cascade downstream of PDGF that sustains proneural glioblastoma cells and suggest that inhibition

173 is could serve as a therapeutic strategy for proneural glioblastoma featuring increased PDGF signalin

174 effects are evident by latent appearance of proneural glioblastoma in adult mice deleted additionall

175 Proneural glioblastoma is defined by an expression patte

176 ted with prolonged survival in patients with proneural glioblastoma, but not with other subtypes of g

177 ogression, similar to those deleted in human proneural glioblastoma.

178 response of glioma cells in a mouse model of proneural glioblastoma.

179 ssion programs, characterize G-CIMP-positive proneural glioblastomas but not other glioblastomas, and

180 Using a mouse model of proneural glioma and comparative transcriptomics, we det

181 e 1 (Usp1) to promote the survival of murine proneural glioma cells.

182 is hypothesis in the RCAS-PDGF-HA/nestin-TvA proneural glioma mouse model, in which p21 facilitates a

183 Using a PDGF-B-driven proneural glioma mouse model, we assessed a panel of tyr

184 ion of tumor progression in a mouse model of proneural glioma.

185 y TAMs as a promising therapeutic target for proneural gliomas and establish the translational potent

186 Proneural gliomas can arise from transformation of glial

187 pressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor ini

188 The PDGF-driven proneural group represents a subset of glioblastoma in w

189 s for specific features of the refinement of proneural groups that had resisted explanation.

190 and pharmacologic inhibition, we found that proneural GSCs are preferentially sensitive to EZH2 disr

191 pressed differentiation of Oli-Neu cells and proneural GSCs.

192 her enhance or inhibit the activities of the proneural helix-loop-helix (HLH) factors Ngn1 (Neurog1),

193 conjunction with radiation in patients with proneural HGG as a new strategy for blocking the emergen

194 Additionally, we isolated primary proneural HGG cells from mouse and human tumors and demo

195 sing a genetically engineered mouse model of proneural HGG.

196 long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive s

197 eling the molecular mechanisms that underlie proneural induction, cell fate determination, axonal tar

198 , showing that PDGFA is sufficient to induce proneural-like gliomas and that additional NF1 loss conv

199 een tumours and control samples, and between proneural-like or mesenchymal-like tumours versus contro

200 esenchymal GBMs arise as, and evolve from, a proneural-like precursor.

201 In Mll1-deficient cells, early proneural Mash1 (also known as Ascl1) and gliogenic Olig

202 erization of GBM allowed classification into proneural, mesenchymal and classical subtypes, and have

203 insic transcriptional subtypes designated as proneural, mesenchymal, and classical.

204 sequence variants, including variants within proneural network genes, exhibits these characteristics

205 experiments, we find that for the Drosophila proneural network, the effect of genomic diversity is da

206 oma (GBM) into four transcriptional classes: proneural, neural, classical, and mesenchymal.

207 Though preliminary, a PDOX model of Proneural/Neural-subtype demonstrated significantly impr

208 t and mouse revealed more cells coexpressing proneural neurogenin targets in human than in other spec

209 or knockout of APLN in orthotopic models of proneural or classical GBM subtypes significantly reduce

210 isolated from patient-derived GSC of either proneural or mesenchymal subtypes.

211 additional genetic interactions between this proneural pathway and Abd-A.

212 These results thus connect the proneural pathway with opsin selection to ensure correct

213 Proneural, perivascular GSCs activated EZH2, whereas mes

214 ere is a functional relationship between the proneural phenotype and the associated genetic alteratio

215 f the transcriptional network underlying the proneural phenotype.

216 Overexpression of the proneural pioneer factor Ascl1 results in a well-defined

217 t canonical Wnt signalling that is active in proneural (PN) but inactive in mesenchymal (MES) GBM, al

218 Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed

219 TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which corre

220 ase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs.

221 ere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subty

222 This proneural potency gradient correlated directly with ATH

223 al programs, with vascular regions showing a proneural profile, and hypoxic regions showing a mesench

224 proliferative cells did not progress beyond proneural progenitor phase.

225 HLH-3, the C. elegans homolog of a mammalian proneural protein (Ascl1) used for in vitro neuronal rep

226 lational mechanism that rapidly extinguishes proneural protein activity in neural precursors.

227 anslational switch governing the duration of proneural protein activity that is required for proper n

228 additional post-translational regulation of proneural protein activity.

229 rosophila neural stem cells), which lack the proneural protein Asense (Ase) but not from Ase-expressi

230 of Hairless Paired Site (SPS) and a specific proneural protein binding site associated with arthropod

231 Thus, a proneural protein controls the complex cellular behaviou

232 We have previously shown that the proneural protein Neurog2 promotes the migration of nasc

233 Here we show that the proneural protein neurogenin 2 (Neurog2), which controls

234 The proneural protein neurogenin 2 (NGN2) is a key transcrip

235 Atonal is a Drosophila proneural protein required for the proper formation of t

236 e switched expression from Asense to a third proneural protein, Atonal.

237 or kinase module acts together with a second proneural protein, HLH-2, and in parallel to HLH-3 to pr

238 dependent post-translational modification of proneural proteins directly regulates neuronal different

239 ess via lysine 509 promotes its synergy with proneural proteins during transcriptional activation and

240 ine at the same position in Scute and Atonal proneural proteins governs the transition from active to

241 transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators.

242 s in the zebrafish inner ear and studied the proneural requirement for cell fate decision within this

243 the median neuroblast stem cell, revealing a proneural role for l(1)sc in midline cells.

244 ibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expressi

245 onally, although transformed cells express a proneural signature, untransformed tumor-associated cell

246 late stages of progression, and preceded the proneural-specific deletions.

247 p110alpha expression was highest in the proneural subtype and this was associated with increased

248 nd that the overall ordering applied for the proneural subtype but differed for mesenchymal samples.

249 s confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype,

250 PDGF) signaling are commonly observed in the proneural subtype of glioblastoma and can drive gliomage

251 ey characteristics of the recently described proneural subtype of glioblastoma multiforme.

252 multiforme (GBM) specimens, primarily of the Proneural subtype, and low 53BP1 expression levels are a

253 LF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFR

254 Moreover, for samples of the proneural subtype, we detected two distinct temporal seq

255 ociated with the classical, mesenchymal, and proneural subtypes of GBM.

256 essing the gene signature of mesenchymal and proneural subtypes of glioblastoma.

257 ylation motif in Senseless reduces Senseless/proneural synergy both in vivo and in cell culture.

258 liomas and that additional NF1 loss converts proneural to the mesenchymal subtype.

259 be a phenotypic switch from PDGFRA-enriched "proneural" to EGFR-enriched "classical" features in glio

260 In particular, the proneural-to-mesenchymal transition (PMT) is associated

261 from an oligodendrocyte precursor-correlated proneural toward an astroglia-associated gene expression

262 pression of Amun decreases expression of the proneural transcription factor Achaete, and sensory orga

263 The proneural transcription factor Ascl1 is upregulated in M

264 ling in GSCs that express high levels of the proneural transcription factor ASCL1 leads to robust neu

265 One such factor, the proneural transcription factor Ascl1, is necessary for r

266 difference in regenerative potential is the proneural transcription factor Ascl1.

267 tified regulatory programme dependent on the proneural transcription factor Asense.

268 nal repressor of Atonal Homolog 1 (Atoh1), a proneural transcription factor essential for cerebellar

269 Mice lacking the proneural transcription factor Math1 (Atoh1) lack multip

270 Mice lacking the proneural transcription factor Math1 (Atoh1) lose neuron

271 The proneural transcription factor neurogenin 1 (neurog1) ha

272 afish olfactory epithelium requires the bHLH proneural transcription factor Neurogenin 1 (Neurog1).

273 The proneural transcription factor Neurogenin 2 (Ngn2) acts

274 The proneural transcription factor Neurogenin3 (Ngn3) plays

275 transcribed divergently from the neighboring proneural transcription factor Pou3f2.

276 Ascl1/Mash1 is a proneural transcription factor previously implicated in

277 direct transcriptional repressor of ATOH1, a proneural transcription factor required for normal cereb

278 We identify an ampullary organ-specific proneural transcription factor, and candidates for the v

279 this question, we used the Atonal family of proneural transcription factors as a model.

280 Proneural transcription factors drive the generation of

281 During development, proneural transcription factors of the basic helix-loop-

282 hibition by Sox2 on Wnt signaling and by the proneural transcription factors on Sox2 mean that each e

283 the control of basic Helix-Loop-Helix (bHLH) proneural transcription factors that play key roles duri

284 drive the ectopic expression of a subset of proneural transcription factors that ultimately define t

285 Our results suggest that proneural transcription factors, such as Neurog1, direct

286 functional neurons by ectopic expression of proneural transcription factors.

287 dependently of Wnt signaling and upregulated proneural transcription factors.

288 isms of action that govern the regulation of proneural transcription factors.

289 r deletions, establishing a link between the proneural transcriptional network and the subtype-specif

290 ase by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with com

291 These factors may support proneural tumor progression and could be potential targe

292 Mice co-transplanted with proneural tumor sphere cells and Prom1(+) endothelium ha

293 In proneural tumors derived from injection of RCAS-PDGF int

294 he different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progen

295 e Cancer Genome Atlas database revealed that proneural tumors with mesenchymal EV signatures or mesen

296 rogeneous signaling mechanisms active in GBM Proneural tumors, with possible clinical relevance.

297 o lateral inhibition and thus limits further proneural upregulation.

298 the physical and molecular underpinnings of proneural wave progression and suggests a generic mechan

299 We show that the proneural wave transiently suppresses Notch activity in

300 Here, we propose that this 'proneural wave' is driven by an excitable reaction-diffu