Shape deformation analysis reveals the temporal dynamics of cell-type-specific homeostatic and pathogenic responses to mutant huntingtin.
C. elegans
Drosophila
computational biology
human
mouse
systems biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 02 2021
23 02 2021
Historique:
received:
18
11
2020
accepted:
31
01
2021
entrez:
23
2
2021
pubmed:
24
2
2021
medline:
29
1
2022
Statut:
epublish
Résumé
Loss of cellular homeostasis has been implicated in the etiology of several neurodegenerative diseases (NDs). However, the molecular mechanisms that underlie this loss remain poorly understood on a systems level in each case. Here, using a novel computational approach to integrate dimensional RNA-seq and in vivo neuron survival data, we map the temporal dynamics of homeostatic and pathogenic responses in four striatal cell types of Huntington's disease (HD) model mice. This map shows that most pathogenic responses are mitigated and most homeostatic responses are decreased over time, suggesting that neuronal death in HD is primarily driven by the loss of homeostatic responses. Moreover, different cell types may lose similar homeostatic processes, for example, endosome biogenesis and mitochondrial quality control in
Identifiants
pubmed: 33618800
doi: 10.7554/eLife.64984
pii: 64984
pmc: PMC7901871
doi:
pii:
Substances chimiques
Htt protein, mouse
0
Huntingtin Protein
0
Banques de données
GEO
['GPL24247', 'GSE152058', 'GPL13112']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R01 NS100802
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS085880
Pays : United States
Informations de copyright
© 2021, Megret et al.
Déclaration de conflit d'intérêts
LM, BG, SS, JC, MW, JA, JR, TV, HW, MH, CN No competing interests declared
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