- EMDB-29074: CryoET tomogram of HD patient iPSC-derived neuron (Q66) -
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基本情報
登録情報
データベース: EMDB / ID: EMD-29074
タイトル
CryoET tomogram of HD patient iPSC-derived neuron (Q66)
マップデータ
Representative IMOD-reconstructed cryoET tomogram of a neurite region in neuron differentiated from induced pluripotent stem cells derived from HD patient with a polyQ tract of length Q=66
試料
細胞: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 66 Qs
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
P01NS092525
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD021600
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
R35NS116872
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: CryoET reveals organelle phenotypes in huntington disease patient iPSC-derived and mouse primary neurons. 著者: Gong-Her Wu / Charlene Smith-Geater / Jesús G Galaz-Montoya / Yingli Gu / Sanket R Gupte / Ranen Aviner / Patrick G Mitchell / Joy Hsu / Ricardo Miramontes / Keona Q Wang / Nicolette R ...著者: Gong-Her Wu / Charlene Smith-Geater / Jesús G Galaz-Montoya / Yingli Gu / Sanket R Gupte / Ranen Aviner / Patrick G Mitchell / Joy Hsu / Ricardo Miramontes / Keona Q Wang / Nicolette R Geller / Cathy Hou / Cristina Danita / Lydia-Marie Joubert / Michael F Schmid / Serena Yeung / Judith Frydman / William Mobley / Chengbiao Wu / Leslie M Thompson / Wah Chiu / 要旨: Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived ...Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD.
ダウンロード / ファイル: emd_29074.map.gz / 形式: CCP4 / 大きさ: 1 GB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Representative IMOD-reconstructed cryoET tomogram of a neurite region in neuron differentiated from induced pluripotent stem cells derived from HD patient with a polyQ tract of length Q=66
ボクセルのサイズ
X=Y=Z: 13.76 Å
密度
最小 - 最大
-3.0 - 3.0
平均 (標準偏差)
0.0039421506 (±0.97008485)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
-512
-512
-128
サイズ
1024
1024
256
Spacing
1024
1024
256
セル
A: 14090.24 Å / B: 14090.24 Å / C: 3522.56 Å α=β=γ: 90.0 °
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添付データ
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試料の構成要素
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全体 : Human neuron differentiated from induced pluripotent stem cells d...
全体
名称: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 66 Qs
要素
細胞: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 66 Qs
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超分子 #1: Human neuron differentiated from induced pluripotent stem cells d...
超分子
名称: Human neuron differentiated from induced pluripotent stem cells derived from HD patient with a huntingtin gene containing a polyQ tract with 66 Qs タイプ: cell / ID: 1 / 親要素: 0 / 詳細: Mitochondria in situ