PMID- 33892814
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20221013
IS  - 2051-5960 (Electronic)
IS  - 2051-5960 (Linking)
VI  - 9
IP  - 1
DP  - 2021 Apr 23
TI  - Enhanced detection of expanded repeat mRNA foci with hybridization chain 
      reaction.
PG  - 73
LID - 10.1186/s40478-021-01169-8 [doi]
LID - 73
AB  - Transcribed nucleotide repeat expansions form detectable RNA foci in patient 
      cells that contribute to disease pathogenesis. The most widely used method for 
      detecting RNA foci, fluorescence in situ hybridization (FISH), is powerful but 
      can suffer from issues related to signal above background. Here we developed a 
      repeat-specific form of hybridization chain reaction (R-HCR) as an alternative 
      method for detection of repeat RNA foci in two neurodegenerative disorders: 
      C9orf72 associated ALS and frontotemporal dementia (C9 ALS/FTD) and Fragile 
      X-associated tremor/ataxia syndrome. R-HCR to both G(4)C(2) and CGG repeats 
      exhibited comparable specificity but > 40 x sensitivity compared to FISH, with 
      better detection of both nuclear and cytoplasmic foci in human C9 ALS/FTD 
      fibroblasts, patient iPSC derived neurons, and patient brain samples. Using 
      R-HCR, we observed that integrated stress response (ISR) activation significantly 
      increased the number of endogenous G(4)C(2) repeat RNA foci and triggered their 
      selective nuclear accumulation without evidence of stress granule co-localization 
      in patient fibroblasts and patient derived neurons. These data suggest that R-HCR 
      can be a useful tool for tracking the behavior of repeat expansion mRNA in C9 
      ALS/FTD and other repeat expansion disorders.
FAU - Glineburg, M Rebecca
AU  - Glineburg MR
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA.
AD  - Department of Respiratory Medicine, Xiangya Hospital, Central South University, 
      Changsha, 410008, China.
FAU - Krans, Amy
AU  - Krans A
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA.
AD  - Veterans Affairs Medical Center, Ann Arbor, MI, USA.
FAU - Tank, Elizabeth M
AU  - Tank EM
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA.
FAU - Barmada, Sami J
AU  - Barmada SJ
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA.
FAU - Todd, Peter K
AU  - Todd PK
AUID- ORCID: 0000-0003-4781-6376
AD  - Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann 
      Arbor, MI, 4005 BSRB48109-2200, USA. Petertod@umich.edu.
AD  - Veterans Affairs Medical Center, Ann Arbor, MI, USA. Petertod@umich.edu.
LA  - eng
GR  - R01 NS097542/NS/NINDS NIH HHS/United States
GR  - P50 HD104463/HD/NICHD NIH HHS/United States
GR  - T32NS00722237/NS/NINDS NIH HHS/United States
GR  - P50HD104463/National Institute of Child Health and Human Development/
GR  - R01NS086810/NS/NINDS NIH HHS/United States
GR  - R01 NS099280/NS/NINDS NIH HHS/United States
GR  - R01 NS113943/NS/NINDS NIH HHS/United States
GR  - BLRD BX004842/U.S. Department of Veterans Affairs/
GR  - R01 NS086810/NS/NINDS NIH HHS/United States
GR  - R01NS099280/NS/NINDS NIH HHS/United States
GR  - I01 BX004842/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210423
PL  - England
TA  - Acta Neuropathol Commun
JT  - Acta neuropathologica communications
JID - 101610673
RN  - 0 (C9orf72 Protein)
RN  - 0 (C9orf72 protein, human)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/*genetics/metabolism/pathology
MH  - C9orf72 Protein/*genetics/metabolism
MH  - Cells, Cultured
MH  - DNA Repeat Expansion/physiology
MH  - Fibroblasts/metabolism/pathology
MH  - Frontotemporal Dementia/*genetics/metabolism/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - RNA, Messenger/*genetics/metabolism
PMC - PMC8063431
OTO - NOTNLM
OT  - Amyotrophic lateral sclerosis
OT  - C9orf72
OT  - FXTAS
OT  - Fragile X
OT  - G3BP
OT  - RNA Gelation
OT  - RNA foci
OT  - Repeat-associated non-AUG (RAN) translation
OT  - Stress granules
EDAT- 2021/04/25 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/04/23
CRDT- 2021/04/24 05:29
PHST- 2021/01/20 00:00 [received]
PHST- 2021/03/27 00:00 [accepted]
PHST- 2021/04/24 05:29 [entrez]
PHST- 2021/04/25 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/04/23 00:00 [pmc-release]
AID - 10.1186/s40478-021-01169-8 [pii]
AID - 1169 [pii]
AID - 10.1186/s40478-021-01169-8 [doi]
PST - epublish
SO  - Acta Neuropathol Commun. 2021 Apr 23;9(1):73. doi: 10.1186/s40478-021-01169-8.