ライフサイエンスコーパス: proplatelet

1 ng and release concludes at the tips of each proplatelet.

2 rays, continuously polymerize throughout the proplatelet.

3 rm of RhoA is substantially downregulated in proplatelets.

4 ) to reduce the work required for generating proplatelets.

5 ecific areas of the marginal tubular-coil in proplatelets.

6 nd forth between round cells and multibodied proplatelets.

7 ation, particularly the inability to produce proplatelets.

8 yocyte (MK) differentiation or generation of proplatelets.

9 ransfer this regulatory system to developing proplatelets.

10 are delivered to and assembled de novo along proplatelets.

11 y on the microtubule arrays of permeabilized proplatelets.

12 arge, polyploid megakaryocytes that produced proplatelets.

13 lizes to microtubule shafts and coils within proplatelets.

14 of CD41(+) fragments similar in size to pre/proplatelets.

15 rane system and a striking inability to form proplatelets.

16 bunit of the 26S proteasome, fail to produce proplatelets.

17 gy with an elevated number of barbell-shaped proplatelets, a recently discovered intermediate stage i

18 ce blood platelets, megakaryocytes elaborate proplatelets, accompanied by expansion of membrane surfa

19 hanisms controlling the decision to initiate proplatelet and platelet formation are unknown.

20 fferentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosi

21 upon reaching a liquid milieu to facilitate proplatelet and platelet formation.

22 n of the spectrin-based membrane skeleton in proplatelet and platelet production in murine megakaryoc

23 l properties of the microenvironment prevent proplatelet and platelet release in the marrow stroma wh

24 lowing myelosuppression led to inappropriate proplatelet and platelet release into the extravascular

25 d platelets are detected only at the ends of proplatelets and not within the platelet-sized beads fou

26 ets by remodeling their cytoplasm first into proplatelets and then into preplatelets, which undergo f

27 tes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extrac

28 and Arp2 were dephosphorylated in MKs making proplatelets, and Arp2 inhibition enhanced proplatelet f

29 led de novo and released only at the ends of proplatelets, and that the complex bending and branching

30 gakaryocyte ploidy and the generation of pre/proplatelets are both increased in culture by pharmacolo

31 Proplatelets are filamentous extensions of terminally di

32 plus-end growth rates of microtubules within proplatelets are highly variable (1.5-23.5 microm/min) a

33 ts suggest that podosomes may have a role in proplatelet arm extension or penetration of basement mem

34 ytes give rise to platelets via extension of proplatelet arms, which are released through the vascula

35 olar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionall

36 omal cells (MSCs) enhanced the production of proplatelet-bearing megakaryocytes (MKs) and platelet-li

37 Constitutive formation of the proplatelet-bearing MK was recently reported to be caspa

38 population was able to efficiently generate proplatelet-bearing MKs and platelet-like particles.

39 roplatelet extension (microtubule-driven) vs proplatelet branching (Arp2/3 and actin polymerization-d

40 d proplatelet formation with a wide range of proplatelet bud sizes, including abnormally large propla

41 atelet bud sizes, including abnormally large proplatelet buds containing incorrect numbers of von Wil

42 in partially colocalize near the membrane of proplatelet buds.

43 shafts as shown by confocal observations of proplatelet buds.

44 ne marrow cell cultures were induced to form proplatelets by exposure to plasma, and the role of vari

45 apacity to convert reversibly into elongated proplatelets by twisting microtubule-based forces that c

46 ized proplatelet system rapidly destabilizes proplatelets, causing blebbing and swelling.

47 rmal megakaryocytes, which generate abundant proplatelets, cells from these mice never produce propla

48 ition, Cib1(-/-) megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on

49 Triton X-100-permeabilized proplatelets containing dynein and its regulatory comple

50 ite the continuous assembly of microtubules, proplatelets continue to elongate when net microtubule a

51 hibition of RhoA is capable of reversing the proplatelet defects mediated by PKCepsilon inhibition.

52 gs suggest an important role for PKCalpha in proplatelet development and suggest that it acts by alte

53 Proplatelets elongate at an average rate of 0.85 microm/

54 ore, we show that microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic d

55 necessary force for microtubule sliding and proplatelet elongation from megakaryocytes.

56 elet production, the underlying mechanism of proplatelet elongation has yet to be resolved.

57 Although the mechanics of proplatelet elongation have been studied, the terminal s

58 lapping microtubules is a vital component of proplatelet elongation.

59 disrupts dynactin-dynein function, inhibits proplatelet elongation.

60 e bidirectionally until they are captured at proplatelet ends.

61 elegant mechanism to increase the numbers of proplatelet ends.

62 atelets, cells from these mice never produce proplatelets, even after prolonged stimulation with c-Mp

63 ubule-based forces that can be visualized in proplatelets expressing GFP-beta1-tubulin.

64 ng PIP2 signaling to regulate processes like proplatelet extension (microtubule-driven) vs proplatele

65 n promoted microtubule-dependent budding and proplatelet extension inside the gel.

66 balance between megakaryocyte retention and proplatelet extension remains largely unknown.

67 r invaginated membrane system maturation and proplatelet extension, because expression of a spectrin

68 The formation of proplatelet extensions from megakaryocytes into bone mar

69 ntact bone marrow to latrunculin-A triggered proplatelet extensions in the interstitial space.

70 g platelets by extending and depositing long proplatelet extensions into the bloodstream.

71 go extensive cytoskeletal remodeling to form proplatelet extensions that eventually produce mature pl

72 bulin expression and organization, decreased proplatelet extensions, and reduced phosphorylation of t

73 lets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines fo

74 platelets by reorganizing the cytoplasm into proplatelet extensions.

75 atelet-sized beads found along the length of proplatelet extensions.

76 granules were underrepresented in MVB II and proplatelet extensions.

77 t/proplatelet interconversion, and (d) model proplatelet fission and platelet release.

78 n that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.

79 s without precluding observations that some "proplatelets" form in the sinusoids of the bone marrow b

80 The process of proplatelet formation (PPF) requires coordinated interac

81 erentiate into MKs that are fully capable of proplatelet formation (PPF).

82 knockdown lead to a strong decrease in human proplatelet formation (PPF).

83 nhibition by peptide significantly decreased proplatelet formation 53%.

84 osphorylation while significantly inhibiting proplatelet formation 84%, suggesting that MARCKS phosph

85 tation is associated with a marked defect in proplatelet formation and a low level in filamin A in me

86 in tubulin dynamics or RhoA activity impairs proplatelet formation and alters platelet morphology.

87 in vitro, GATA-1s-expressing cells displayed proplatelet formation and other features of terminal mat

88 In particular, hGH is potent in facilitating proplatelet formation and platelet production from cultu

89 e to the capillary-rich vascular niche where proplatelet formation and platelet release occurs.

90 pillary-rich vascular niche is essential for proplatelet formation and platelet release.

91 r to exposure to CCL5 reversed the augmented proplatelet formation and ploidy, suggesting that CCL5 i

92 Megakaryocytes in Jak2VF CH showed elevated proplatelet formation and release, increasing prothrombo

93 ation and organelle distribution, as well as proplatelet formation and sizing.

94 n, selective Mylk inhibition by ML7 affected proplatelet formation and stabilization and resulted in

95 t correlation between thrombocytopoiesis and proplatelet formation and suggest that the latter repres

96 medium, MC-grown MKs displayed twice as much proplatelet formation as cells grown in liquid culture.

97 d normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylat

98 Proplatelet formation by Hyal-2 knockout megakaryocytes

99 megakaryocyte differentiation, and disrupts proplatelet formation by inducing abnormal tubulin organ

100 e marrow: promoting megakaryocyte growth and proplatelet formation by interaction with C-type lectin-

101 ia virus oncogene (MPL) pathway and impaired proplatelet formation by MKs.

102 We further show that proplatelet formation by normal megakaryocytes and its a

103 toskeletal alterations resulting in impaired proplatelet formation by Trpm7(fl/fl-Pf4Cre) MKs, which

104 n that the physiologic mechanisms that drive proplatelet formation can be recapitulated in cell-free

105 The results indicate that disrupted proplatelet formation contributes to the macrothrombocyt

106 K inhibition completely rescued the in vitro proplatelet formation defect.

107 We show that proplatelet formation first occurs in a unique and previ

108 n the one hand, recent findings suggest that proplatelet formation from bone marrow-derived MKs is no

109 The R1213* variant was linked to reduced proplatelet formation from cultured MKs, cell clustering

110 vitro, shear stress was shown to accelerate proplatelet formation from mature megakaryocytes (Mks).

111 some clustering as an important initiator of proplatelet formation from MKs.

112 suggesting that CCL5 increases MK ploidy and proplatelet formation in a CCR5-dependent manner.

113 gic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes.

114 of exogenous hyaluronidase rescued deficient proplatelet formation in murine and human megakaryocytes

115 ulin in isolation does not, however, restore proplatelet formation in the defective megakaryocytes, i

116 rotein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhib

117 ovel insights into the mechanisms leading to proplatelet formation in vitro and in vivo will be revie

118 ors similarly reduce MK polyploidization and proplatelet formation in vitro and platelet levels in vi

119 Moreover, proplatelet formation in vitro by transgenic megakaryocy

120 ciency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in

121 , PKCepsilon is a critical mediator of mouse proplatelet formation in vitro.

122 ly, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro.

123 These results confirm the concept of proplatelet formation in vivo and are consistent with th

124 ted role of alpha2beta1 in MK maturation and proplatelet formation in vivo.

125 thin bone marrow and a significantly reduced proplatelet formation in vivo.

126 Here we report that proplatelet formation is a process that can be divided i

127 Proplatelet formation is a tightly orchestrated process

128 Defective proplatelet formation is considered to be the principal

129 dult environments, the frequency and rate of proplatelet formation is incompatible with the physiolog

130 Forced cell cycle arrest in G(1) increased proplatelet formation not only in vitro but also in vivo

131 emarcation membrane system) polarization and proplatelet formation of Ck1alphaPf4Delta/Pf4Delta MKs,

132 Reduction in proplatelet formation potential is associated with a def

133 Proplatelet formation releases into the bloodstream bead

134 Proplatelet formation requires a profound reorganization

135 upstream and downstream pathways involved in proplatelet formation should provide greater insights in

136 production assays had a higher capacity for proplatelet formation than MKs from other organs.

137 vere quantitative and qualitative defects in proplatelet formation that mimic findings in gm/gm cells

138 In transcriptome profiling, the defect in proplatelet formation was associated with an aberrant ac

139 Abnormal proplatelet formation was confirmed in the propositus's

140 d F-actin under mechanical constraints while proplatelet formation was inhibited.

141 Proplatelet formation was reduced in megakaryocytes from

142 The defect in proplatelet formation was rescued in vitro by lentiviral

143 er, cultured Tmod3(-/-) MKs exhibit impaired proplatelet formation with a wide range of proplatelet b

144 est that Rab27b in particular may coordinate proplatelet formation with granule transport, possibly b

145 During proplatelet formation, a relatively homogeneous content

146 tin polymerization causes similar arrests in proplatelet formation, acting at a step beyond expansion

147 al liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completel

148 e what are the forces that determine barbell-proplatelet formation, and how is the final platelet siz

149 ght in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification

150 Whereas MK maturation, proplatelet formation, and platelet production under in

151 n MK cytoskeletal dynamics and polarization, proplatelet formation, and polyploidization, thus highli

152 data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wn

153 on, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia.

154 f MK cytoskeletal dynamics and polarization, proplatelet formation, and thrombopoiesis.

155 of platelet generation from megakaryocytes (proplatelet formation, cytoplasmic fragmentation, and me

156 In cultures containing active proplatelet formation, cytoplasmic polymerized actin was

157 ciency did not affect MK polyploidisation or proplatelet formation, it dampened MK granule biogenesis

158 er insights into the function of PKCalpha in proplatelet formation, its subcellular localization was

159 alphaIIbbeta3-H723 receptor causes abnormal proplatelet formation, leading to incorrect sizing of pl

160 Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (

161 SLPI(-/-) mice show intact proplatelet formation, platelet numbers and shape, and m

162 iciency in megakaryopoiesis, specifically in proplatelet formation, resulting in profound thrombocyto

163 rmal cell deformation and strongly decreased proplatelet formation, similarly to features observed fo

164 e propose that membrane budding, rather than proplatelet formation, supplies the majority of the plat

165 beta1-tubulin-null mice show reduced proplatelet formation, thrombocytopenia, and platelet sp

166 ; however, only the latter exhibited reduced proplatelet formation, thrombopoietin, and integrin sign

167 pact on the estradiol signaling required for proplatelet formation, thus resulting in thrombocytopeni

168 ering following mitosis, closely followed by proplatelet formation, which exclusively occurred in G(1

169 1 (KIFC1) impaired clustering and subsequent proplatelet formation, while KIFC1-deficient mice exhibi

170 on from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the pe

171 ocytes display greater migratory ability and proplatelet formation.

172 vestigate a potential role for PKCepsilon in proplatelet formation.

173 w and mature MKs displayed a major defect in proplatelet formation.

174 and diameter and thickness determine barbell-proplatelet formation.

175 with exaggerated megakaryocytopoiesis and/or proplatelet formation.

176 leading to both a defect in ploidization and proplatelet formation.

177 icating that PDK1 is critically required for proplatelet formation.

178 ies of steps, including polyploidization and proplatelet formation.

179 ntiation but also impairing MK migration and proplatelet formation.

180 by a negative regulatory effect on premature proplatelet formation.

181 nase ROCK1/2 restored a normal phenotype and proplatelet formation.

182 TSP2 in vitro affects MK differentiation and proplatelet formation.

183 bozymes specific for PKCalpha each inhibited proplatelet formation.

184 ctin reorganization, PKC relocalization, and proplatelet formation.

185 ase, or protein kinase A failed to affect MK proplatelet formation.

186 ither GPIb or Cdc42 impairs transendothelial proplatelet formation.

187 ation between thrombocytopoiesis in vivo and proplatelet formation.

188 l-developed demarcation membrane system, and proplatelet formation.

189 rogram of enlargement, polyploidization, and proplatelet formation.

190 iferation and polyploidization and decreases proplatelet formation.

191 MKs showed reduced colony and proplatelet formation.

192 dult life without induction of cell death or proplatelet formation.

193 g proplatelets, and Arp2 inhibition enhanced proplatelet formation.

194 r, very little is known about what regulates proplatelet formation.

195 ggesting that MARCKS phosphorylation reduces proplatelet formation.

196 s inhibition prevented MC-mediated increased proplatelet formation.

197 akaryocyte maturation, polyploidization, and proplatelet formation.

198 ensuring proper execution of actin-dependent proplatelet formation.

199 horylation, which subsequently downregulates proplatelet formation; both MARCKS and Arp2 were dephosp

200 ) mice to probe the direct role of MARCKS in proplatelet formation; MARCKS KO MKs displayed significa

201 t that it acts by altering actin dynamics in proplatelet-forming MKs.

202 In contrast, the abnormally large proplatelets from Tmod3(-/-) MKs show increased F-actin

203 By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of

204 y revealed that, like circulating platelets, proplatelets have a dense membrane skeleton, the main fi

205 dition of rhodamine-tubulin to permeabilized proplatelets, immunofluorescence microscopy of the micro

206 resence of circular-preplatelets and barbell-proplatelets in blood, and two fundamental questions in

207 e quantify circular-preplatelets and barbell-proplatelets in human blood in high-resolution fluoresce

208 lowing blood, resulting in the appearance of proplatelets in peripheral blood.

209 latelet production and validate the study of proplatelets in probing the underlying mechanisms.

210 The failure to produce proplatelets in proteasome-inhibited megakaryocytes was

211 Preplatelets convert into barbell-shaped proplatelets in vitro to undergo repeated abscissions th

212 ctor 1alpha (SDF1alpha) and the formation of proplatelets in vitro were abolished by dasatinib.

213 ts in SDF1-driven migration and formation of proplatelets in vitro.

214 ever, visualization of platelet release from proplatelets in vivo has remained elusive.

215 cytometry differentiated in vitro to produce proplatelets, independent of thrombopoietin stimulation,

216 polarization and produced significantly less proplatelets, indicating that PDK1 is critically require

217 Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow p

218 toskeletal mechanics involved in preplatelet/proplatelet interconversion, and (d) model proplatelet f

219 arrow (BM) toward the vasculature, extending proplatelets into sinusoids, where circulating blood pro

220 hrough the release of long, microtubule-rich proplatelets into vessel sinusoids.

221 (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids.

222 MKs), which extend protrusions, or so-called proplatelets, into bone marrow sinusoids.

223 extend long branching processes, designated proplatelets, into sinusoidal blood vessels where they u

224 erate platelets by extending long processes, proplatelets, into sinusoidal blood vessels.

225 ing long cytoplasmic protrusions, designated proplatelets, into sinusoidal blood vessels.

226 Movement of organelles along proplatelets involves 2 mechanisms: organelles travel al

227 CKS KO MKs displayed significantly decreased proplatelet levels.

228 CIP4, not WASP, expression resulted in fewer proplatelet-like extensions.

229 ief inhibition generates highly distensible, proplatelet-like projections that fragment readily under

230 ates a signal that leads to the formation of proplatelet-like protrusions in transfected CHO cells.

231 erved as sessile cells that extended dynamic proplatelet-like protrusions into microvessels.

232 ubules is necessary to support the enlarging proplatelet mass, the sliding of overlapping microtubule

233 ion have been studied, the terminal steps of proplatelet maturation and platelet release remain poorl

234 re cells, has been proposed as the source of proplatelet membranes.

235 In immature megakaryocytes lacking proplatelets, microtubule plus-ends initiate and grow by

236 karyocyte cytoskeleton at specific stages of proplatelet morphogenesis and correlated these structure

237 omplex bending and branching observed during proplatelet morphogenesis represents an elegant mechanis

238 PKCepsilon inhibition resulted in lower proplatelet numbers and larger diameter platelets in cul

239 The release of platelets from the ends of proplatelets occurs at an increasing rate in time during

240 the initial protrusion further elongates as proplatelet or buds to release platelets.

241 and fetal liver-derived Dnm2-null MKs formed proplatelets poorly in vitro, showing that DNM2-dependen

242 MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed n

243 at miR-125a-5p positively regulated human MK proplatelet (PP) formation in vitro.

244 Growth and extension of proplatelet processes is associated with repeated bendin

245 d assumptions, time-lapse microscopy reveals proplatelet processes to be extremely dynamic structures

246 es of microtubules to elongate and form thin proplatelet processes with bulbous ends; these contain a

247 production occurs after the formation of MK proplatelet processes.

248 t partly due to a defect in the formation of proplatelet-producing megakaryocytes.

249 ion and to an increased capacity to generate proplatelet-producing MKs and platelet-like elements ult

250 d the proteome and transcriptome of round vs proplatelet-producing MKs by 2D difference gel electroph

251 , which was upregulated 3.4- and 5.7-fold in proplatelet-producing MKs in 2D DIGE and polysome profil

252 releasate from activated platelets increased proplatelet production by 47%.

253 MKs cultured with recombinant CCL5 increased proplatelet production by 50% and had significantly high

254 thway suggested that CCL5/CCR5 may influence proplatelet production by suppressing apoptosis.

255 In vitro, proplatelet production from differentiating MKs was enha

256 r ability to quantify the rate and extent of proplatelet production have restricted the field to qual

257 DM1 affect megakaryocyte differentiation and proplatelet production may yield strategies to manage dr

258 n BM or NMIIA activity and assembly prior to proplatelet production remain unanswered.

259 Proplatelet production represents a terminal stage of me

260 e and extent of megakaryocyte maturation and proplatelet production under live culture conditions for

261 t initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platele

262 lating TPO signaling and later by augmenting proplatelet production.

263 , which ultimately translates into increased proplatelet production.

264 However, the number of proplatelet protrusions was reduced in CIP4-null, but no

265 migration toward the vasculature, impairing proplatelet release and causing macrothrombocytopenia.

266 soids and limit transendothelial crossing to proplatelets remain unknown.

267 nto the sinusoid circulation before terminal proplatelet remodeling.

268 lle traffic along microtubular tracks in the proplatelet shafts as shown by confocal observations of

269 latelets with abnormally large swellings and proplatelet shafts that generated giant platelets in cul

270 activity resulted in defective intravascular proplatelet shedding, the final stage of thrombopoiesis.

271 1P(1) receptor is required for the growth of proplatelet strings in the bloodstream and the shedding

272 aginated membranes and in the maintenance of proplatelet structure.

273 Megakaryocytes readily produce proplatelet structures in vitro; however, visualization

274 These proplatelets subsequently fragment into functional plate

275 shear facilitates fragmentation to large pre/proplatelets, suggesting that fluid stresses and myosin-

276 srupting fragment into a novel permeabilized proplatelet system rapidly destabilizes proplatelets, ca

277 the cytoplasm of human megakaryocytes and in proplatelets that extend from megakaryocytes.

278 openia resulting from a defect in generating proplatelets, the immediate precursors of blood platelet

279 bules in the cell periphery, where they form proplatelets, the immediate precursors of platelets, in

280 ia, and their megakaryocytes fail to produce proplatelets, the microtubule-based precursors of blood

281 s with the microenvironment before extending proplatelets through sinusoids to deliver platelets in t

282 ile extending cytoplasmic protrusions called proplatelets through the sinusoidal endothelial barrier.

283 transferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate

284 travascular megakaryocyte extensions, termed proplatelets, to control platelet production.

285 ocytopenia and is also diffuse in normal pre/proplatelets treated with inhibitor that blocks in vitro

286 asing rate in time during culture, as larger proplatelets undergo successive fission, and is potentia

287 loss of transcription factor GATA-1 produce proplatelets very rarely.

288 nce was normal and differentiation of MKs to proplatelets was unimpaired in hGPIbalphaFW mice.

289 To elucidate this process, released proplatelets were isolated, and their conversion into in

290 rganelles are sent from the cell body to the proplatelets where they move bidirectionally until they

291 cyte differentiation and remains elevated in proplatelets, whereas the active form of RhoA is substan

292 sed from intermediate structures, designated proplatelets, which are long, tubelike extensions of the

293 fewer branches that produce fewer and larger proplatelets, which is phenocopied in mouse Myh9-RD mode

294 convert their cytoplasm into long, branched proplatelets, which remodel into blood platelets.

295 B resulted in the production of ESC-derived proplatelets with abnormally large swellings and proplat

296 luorescence recovery after photobleaching in proplatelets with fluorescence-tagged beta1-tubulin.

297 R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds.

298 MYH9-RD patient MKs have proplatelets with thicker and fewer branches that produc

299 ng thrombopoiesis, megakaryocytes (MKs) form proplatelets within the bone marrow (BM) and release pla

300 out thrombopoiesis megakaryocytes (MKs) form proplatelets within the bone marrow (BM) and release pla