ライフサイエンスコーパス: proneural

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

2 btype (i.e., classical, mesenchymal, neural, 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 egulators including binding sites for Su(H), proneural, and E(spl) basic-helix-loop-helix (bHLH) prot

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

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

29 the PK2 gene is a functional target gene of proneural basic helix-loop-helix (bHLH) factors.

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

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

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

33 Here we report that proneural basic helix-loop-helix (bHLH) transcription fa

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

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

36 xclusive function of dimers formed between a proneural basic helix-loop-helix factor and a specific E

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

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

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

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

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

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

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

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

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

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

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

48 Mechanistically, proneural bHLH factors regulate the expression of genes

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

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

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

52 of proneural ectoderm independently from the proneural bHLH genes.

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

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

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

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

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

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

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

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

61 Proneural class GBM had significantly lower levels of co

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

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

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

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

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

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

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

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

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

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

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

73 factor Atonal (Ato) in spatial patterning of proneural clusters in the morphogenetic furrow.

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

75 In the proneural clusters that give rise to Drosophila mechanos

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

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

78 lls, including those adjacent to SOPs within proneural clusters, suggesting that miR-9a normally inhi

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

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

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

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

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

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

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

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

87 The proneural factor Ascl1 controls multiple steps of neurog

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

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

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

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

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

93 orm ectopic neurons when supplemented with a proneural factor.

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

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

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

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

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

99 We propose that proteins interacting with proneural factors confer such specificity.

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

101 The proneural factors Lethal of scute and Asense differentia

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

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

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

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

106 Proneural factors represent <10 transcriptional regulato

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

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

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

110 ther than bHLH proteins can also perform the proneural function in the Drosophila peripheral nervous

111 pathway confirm that atoh1 genes have early proneural function.

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

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

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

115 prises several molecular subtypes, including proneural GBM.

116 ated with enhanced survival in patients with proneural GBM.

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

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

119 quivalence group marked by expression of the proneural gene Atoh1.

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

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

122 n of ommatidia through the activities of the proneural gene atonal (ato) in the founding R8 photorece

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

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

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

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

127 gate the mechanisms involved in establishing proneural gene expression in the primordia of a group of

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

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

130 vation by Hedgehog induces expression of the proneural gene lethal of scute in the most anterior midl

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

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

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

134 The proneural gene Neurog2 is expressed in progenitors throu

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

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

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

138 show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expr

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

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

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

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

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

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

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

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

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

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

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

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

151 Proneural genes encode transcriptional activators of the

152 Proneural genes encoding basic helix-loop-helix transcri

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

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

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

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

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

158 The proneural genes Neurog2 and Ascl1 cooperate in progenito

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

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

161 Proneural genes thus act in a context-dependent fashion

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

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

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

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

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

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

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

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

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

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

172 t and neuronal fates by controlling specific proneural genes.

173 cells depends on the accurate expression of proneural genes.

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

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

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

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

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

179 Proneural glioblastoma is defined by an expression patte

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

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

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

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

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

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

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

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

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

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

190 Proneural gliomas can arise from transformation of glial

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

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

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

194 ectopic Ato expression in the space between proneural groups.

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

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

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

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

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

200 sing a genetically engineered mouse model of proneural HGG.

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

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

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

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

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

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

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

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

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

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

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

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

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

214 Proneural, perivascular GSCs activated EZH2, whereas mes

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

216 f the transcriptional network underlying the proneural phenotype.

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

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

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

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

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

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

223 This proneural potency gradient correlated directly with ATH

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

225 proliferative cells did not progress beyond proneural progenitor phase.

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

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

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

229 additional post-translational regulation of proneural protein activity.

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

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

232 Thus, a proneural protein controls the complex cellular behaviou

233 Here, we demonstrate that the proneural protein Mash1 and the POU proteins Brn1 and Br

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

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

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

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

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

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

240 The basic helix-loop-helix (bHLH) proneural proteins Achaete and Scute cooperate with the

241 e the ability of Senseless to synergize with proneural proteins and to induce sensory organ formation

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

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

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

245 Proneural proteins play a central role in vertebrate neu

246 gulate and of the factors that interact with proneural proteins to activate a neurogenic program.

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

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

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

250 eless, together with Daughterless, plays the proneural role for the wing margin mechanosensory precur

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

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

253 paired sites and the Su(H) paired site plus proneural site (SPS + A) architecture are completely con

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

270 The proneural transcription factor Ascl1 is upregulated in M

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

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

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

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

275 solated proteins that interact with Math1, a proneural transcription factor essential for the establi

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

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

278 The proneural transcription factor neurogenin 1 (neurog1) ha

279 The proneural transcription factor Neurogenin 2 (Ngn2) acts

280 The proneural transcription factor Neurogenin3 (Ngn3) plays

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

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

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

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

285 Proneural transcription factors drive the generation of

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

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

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

289 dependently of Wnt signaling and upregulated proneural transcription factors.

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

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

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

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

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

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

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

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

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

299 o lateral inhibition and thus limits further proneural upregulation.

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