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Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B

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Harvard

Zhang, C-Y, Schmid, B, Nikolaisen, NK, Rasmussen, MA, Aldana, BI, Agger, M, Calloe, K, Stummann, TC, Larsen, HM, Nielsen, TT, Huang, J, Xu, F, Liu, X, Bolund, L, Meyer, M, Bak, LK, Waagepetersen, HS, Luo, Y, Nielsen, JE, Holst, B, Clausen, C, Hyttel, P, Freude, KK & FReJA Consortium 2017, 'Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B', Stem Cell Reviews and Reports, bind 8, nr. 3, s. 648-658. https://doi.org/10.1016/j.stemcr.2017.01.012

APA

Zhang, C-Y., Schmid, B., Nikolaisen, N. K., Rasmussen, M. A., Aldana, B. I., Agger, M., Calloe, K., Stummann, T. C., Larsen, H. M., Nielsen, T. T., Huang, J., Xu, F., Liu, X., Bolund, L., Meyer, M., Bak, L. K., Waagepetersen, H. S., Luo, Y., Nielsen, J. E., ... FReJA Consortium (2017). Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. Stem Cell Reviews and Reports, 8(3), 648-658. https://doi.org/10.1016/j.stemcr.2017.01.012

CBE

Zhang C-Y, Schmid B, Nikolaisen NK, Rasmussen MA, Aldana BI, Agger M, Calloe K, Stummann TC, Larsen HM, Nielsen TT, Huang J, Xu F, Liu X, Bolund L, Meyer M, Bak LK, Waagepetersen HS, Luo Y, Nielsen JE, Holst B, Clausen C, Hyttel P, Freude KK, FReJA Consortium. 2017. Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. Stem Cell Reviews and Reports. 8(3):648-658. https://doi.org/10.1016/j.stemcr.2017.01.012

MLA

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Author

Zhang, Chen-Yu ; Schmid, Benjamin ; Nikolaisen, Nanett K ; Rasmussen, Mikkel Aabech ; Aldana, Blanca I ; Agger, Mikkel ; Calloe, Kirstine ; Stummann, Tina C ; Larsen, Hjalte M ; Nielsen, Troels T ; Huang, Jinrong ; Xu, Fengping ; Liu, Xin ; Bolund, Lars ; Meyer, Morten ; Bak, Lasse K ; Waagepetersen, Helle S ; Luo, Yonglun ; Nielsen, Jørgen E ; Holst, Bjørn ; Clausen, Christian ; Hyttel, Poul ; Freude, Kristine K ; FReJA Consortium. / Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. I: Stem Cell Reviews and Reports. 2017 ; Bind 8, Nr. 3. s. 648-658.

Bibtex

@article{7d709b52c29441efa899944dccdfb078,
title = "Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B",
abstract = "The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs) were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development.",
keywords = "Journal Article",
author = "Chen-Yu Zhang and Benjamin Schmid and Nikolaisen, {Nanett K} and Rasmussen, {Mikkel Aabech} and Aldana, {Blanca I} and Mikkel Agger and Kirstine Calloe and Stummann, {Tina C} and Larsen, {Hjalte M} and Nielsen, {Troels T} and Jinrong Huang and Fengping Xu and Xin Liu and Lars Bolund and Morten Meyer and Bak, {Lasse K} and Waagepetersen, {Helle S} and Yonglun Luo and Nielsen, {J{\o}rgen E} and Bj{\o}rn Holst and Christian Clausen and Poul Hyttel and Freude, {Kristine K} and {FReJA Consortium}",
note = "Copyright {\textcopyright} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = mar,
day = "14",
doi = "10.1016/j.stemcr.2017.01.012",
language = "English",
volume = "8",
pages = "648--658",
journal = "Stem Cell Reviews and Reports",
issn = "1550-8943",
publisher = "Humana Press, Inc",
number = "3",

}

RIS

TY - JOUR

T1 - Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B

AU - Zhang, Chen-Yu

AU - Schmid, Benjamin

AU - Nikolaisen, Nanett K

AU - Rasmussen, Mikkel Aabech

AU - Aldana, Blanca I

AU - Agger, Mikkel

AU - Calloe, Kirstine

AU - Stummann, Tina C

AU - Larsen, Hjalte M

AU - Nielsen, Troels T

AU - Huang, Jinrong

AU - Xu, Fengping

AU - Liu, Xin

AU - Bolund, Lars

AU - Meyer, Morten

AU - Bak, Lasse K

AU - Waagepetersen, Helle S

AU - Luo, Yonglun

AU - Nielsen, Jørgen E

AU - Holst, Bjørn

AU - Clausen, Christian

AU - Hyttel, Poul

AU - Freude, Kristine K

AU - FReJA Consortium

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017/3/14

Y1 - 2017/3/14

N2 - The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs) were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development.

AB - The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs) were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development.

KW - Journal Article

U2 - 10.1016/j.stemcr.2017.01.012

DO - 10.1016/j.stemcr.2017.01.012

M3 - Journal article

C2 - 28216144

VL - 8

SP - 648

EP - 658

JO - Stem Cell Reviews and Reports

JF - Stem Cell Reviews and Reports

SN - 1550-8943

IS - 3

ER -

ID: 51500951