Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

Research output: Contribution to journal › Journal article › Research › peer-review

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Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. / Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie; Li, Xiaojie; Chandler-Militello, Devin; Mauceri, Joseph; Burm, Hayley B.; Toner, Michael; Osipovitch, Mikhail; Jim Xu, Qiwu; Ding, Fengfei; Wang, Fushun; Kang, Ning; Kang, Jian; Curtin, Paul C.; Brunner, Daniela; Windrem, Martha S.; Munoz-Sanjuan, Ignacio; Nedergaard, Maiken; Goldman, Steven A.

In: Nature Communications, Vol. 7, 11758, 07.06.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Benraiss, A, Wang, S, Herrlinger, S, Li, X, Chandler-Militello, D, Mauceri, J, Burm, HB, Toner, M, Osipovitch, M, Jim Xu, Q, Ding, F, Wang, F, Kang, N, Kang, J, Curtin, PC, Brunner, D, Windrem, MS, Munoz-Sanjuan, I, Nedergaard, M & Goldman, SA 2016, 'Human glia can both induce and rescue aspects of disease phenotype in Huntington disease', Nature Communications, vol. 7, 11758. https://doi.org/10.1038/ncomms11758

APA

Benraiss, A., Wang, S., Herrlinger, S., Li, X., Chandler-Militello, D., Mauceri, J., Burm, H. B., Toner, M., Osipovitch, M., Jim Xu, Q., Ding, F., Wang, F., Kang, N., Kang, J., Curtin, P. C., Brunner, D., Windrem, M. S., Munoz-Sanjuan, I., Nedergaard, M., & Goldman, S. A. (2016). Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. Nature Communications, 7, [11758]. https://doi.org/10.1038/ncomms11758

Vancouver

Benraiss A, Wang S, Herrlinger S, Li X, Chandler-Militello D, Mauceri J et al. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. Nature Communications. 2016 Jun 7;7. 11758. https://doi.org/10.1038/ncomms11758

Author

Benraiss, Abdellatif ; Wang, Su ; Herrlinger, Stephanie ; Li, Xiaojie ; Chandler-Militello, Devin ; Mauceri, Joseph ; Burm, Hayley B. ; Toner, Michael ; Osipovitch, Mikhail ; Jim Xu, Qiwu ; Ding, Fengfei ; Wang, Fushun ; Kang, Ning ; Kang, Jian ; Curtin, Paul C. ; Brunner, Daniela ; Windrem, Martha S. ; Munoz-Sanjuan, Ignacio ; Nedergaard, Maiken ; Goldman, Steven A. / Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. In: Nature Communications. 2016 ; Vol. 7.

Bibtex

@article{27af4b1a69524dcaad7910fed20c457f,
title = "Human glia can both induce and rescue aspects of disease phenotype in Huntington disease",
abstract = "The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.",
keywords = "Journal Article",
author = "Abdellatif Benraiss and Su Wang and Stephanie Herrlinger and Xiaojie Li and Devin Chandler-Militello and Joseph Mauceri and Burm, {Hayley B.} and Michael Toner and Mikhail Osipovitch and {Jim Xu}, Qiwu and Fengfei Ding and Fushun Wang and Ning Kang and Jian Kang and Curtin, {Paul C.} and Daniela Brunner and Windrem, {Martha S.} and Ignacio Munoz-Sanjuan and Maiken Nedergaard and Goldman, {Steven A.}",
year = "2016",
month = jun,
day = "7",
doi = "10.1038/ncomms11758",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

AU - Benraiss, Abdellatif

AU - Wang, Su

AU - Herrlinger, Stephanie

AU - Li, Xiaojie

AU - Chandler-Militello, Devin

AU - Mauceri, Joseph

AU - Burm, Hayley B.

AU - Toner, Michael

AU - Osipovitch, Mikhail

AU - Jim Xu, Qiwu

AU - Ding, Fengfei

AU - Wang, Fushun

AU - Kang, Ning

AU - Kang, Jian

AU - Curtin, Paul C.

AU - Brunner, Daniela

AU - Windrem, Martha S.

AU - Munoz-Sanjuan, Ignacio

AU - Nedergaard, Maiken

AU - Goldman, Steven A.

PY - 2016/6/7

Y1 - 2016/6/7

N2 - The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.

AB - The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.

KW - Journal Article

U2 - 10.1038/ncomms11758

DO - 10.1038/ncomms11758

M3 - Journal article

C2 - 27273432

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11758

ER -

ID: 164971413