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 ecific areas of the marginal tubular-coil in proplatelets.

4 nd forth between round cells and multibodied proplatelets.

5 yocyte (MK) differentiation or generation of proplatelets.

6 ransfer this regulatory system to developing proplatelets.

7 are delivered to and assembled de novo along proplatelets.

8 y on the microtubule arrays of permeabilized proplatelets.

9 arge, polyploid megakaryocytes that produced proplatelets.

10 lizes to microtubule shafts and coils within proplatelets.

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

12 rane system and a striking inability to form proplatelets.

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

14 rm of RhoA is substantially downregulated in proplatelets.

15 ) to reduce the work required for generating proplatelets.

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

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

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

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

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

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

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

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

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

25 Proplatelets are filamentous extensions of terminally di

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

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

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

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

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

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

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

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

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

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

36 in partially colocalize near the membrane of proplatelet buds.

37 shafts as shown by confocal observations of proplatelet buds.

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

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

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

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

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

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

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

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

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

47 Proplatelets elongate at an average rate of 0.85 microm/

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

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

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

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

52 lapping microtubules is a vital component of proplatelet elongation.

53 disrupts dynactin-dynein function, inhibits proplatelet elongation.

54 e bidirectionally until they are captured at proplatelet ends.

55 elegant mechanism to increase the numbers of proplatelet ends.

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

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

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

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

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

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

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

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

64 platelets by reorganizing the cytoplasm into proplatelet extensions.

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

66 granules were underrepresented in MVB II and proplatelet extensions.

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

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

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

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

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

72 nhibition by peptide significantly decreased proplatelet formation 53%.

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

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

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

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

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

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

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

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

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

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

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

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

85 Proplatelet formation by Hyal-2 knockout megakaryocytes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

102 Moreover, proplatelet formation in vitro by transgenic megakaryocy

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

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

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

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

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

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

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

110 Proplatelet formation is a tightly orchestrated process

111 Proplatelet formation requires a profound reorganization

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

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

114 Abnormal proplatelet formation was confirmed in the propositus's

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

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

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

118 During proplatelet formation, a relatively homogeneous content

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

136 vestigate a potential role for PKCepsilon in proplatelet formation.

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

138 and diameter and thickness determine barbell-proplatelet formation.

139 with exaggerated megakaryocytopoiesis and/or proplatelet formation.

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

141 ies of steps, including polyploidization and proplatelet formation.

142 ntiation but also impairing MK migration and proplatelet formation.

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

144 by a negative regulatory effect on premature proplatelet formation.

145 ggesting that MARCKS phosphorylation reduces proplatelet formation.

146 s inhibition prevented MC-mediated increased proplatelet formation.

147 TSP2 in vitro affects MK differentiation and proplatelet formation.

148 bozymes specific for PKCalpha each inhibited proplatelet formation.

149 ctin reorganization, PKC relocalization, and proplatelet formation.

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

151 ation between thrombocytopoiesis in vivo and proplatelet formation.

152 ither GPIb or Cdc42 impairs transendothelial proplatelet formation.

153 rogram of enlargement, polyploidization, and proplatelet formation.

154 akaryocyte maturation, polyploidization, and proplatelet formation.

155 ensuring proper execution of actin-dependent proplatelet formation.

156 g proplatelets, and Arp2 inhibition enhanced proplatelet formation.

157 ocytes display greater migratory ability and proplatelet formation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

180 CKS KO MKs displayed significantly decreased proplatelet levels.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

198 production occurs after the formation of MK proplatelet processes.

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

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

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

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

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

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

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

206 In vitro, proplatelet production from differentiating MKs was enha

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

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

209 Proplatelet production represents a terminal stage of me

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

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

212 lating TPO signaling and later by augmenting proplatelet production.

213 , which ultimately translates into increased proplatelet production.

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

215 soids and limit transendothelial crossing to proplatelets remain unknown.

216 nto the sinusoid circulation before terminal proplatelet remodeling.

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

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

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

220 1P(1) receptor is required for the growth of proplatelet strings in the bloodstream and the shedding

221 aginated membranes and in the maintenance of proplatelet structure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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