TY - JOUR
T1 - Perturbed actin cap as a new personalized biomarker in primary fibroblasts of Huntington’s disease patients
AU - Gharaba, Saja
AU - Paz, Omri
AU - Feld, Lea
AU - Abashidze, Anastasia
AU - Weinrab, Maydan
AU - Muchtar, Noam
AU - Baransi, Adam
AU - Shalem, Aviv
AU - Sprecher, Uri
AU - Wolf, Lior
AU - Wolfenson, Haguy
AU - Weil, Miguel
N1 - Publisher Copyright:
Copyright © 2023 Gharaba, Paz, Feld, Abashidze, Weinrab, Muchtar, Baransi, Shalem, Sprecher, Wolf, Wolfenson and Weil.
PY - 2023/1/18
Y1 - 2023/1/18
N2 - Primary fibroblasts from patient’s skin biopsies are directly isolated without any alteration in the genome, retaining in culture conditions their endogenous cellular characteristics and biochemical properties. The aim of this study was to identify a distinctive cell phenotype for potential drug evaluation in fibroblasts from Huntington’s Disease (HD) patients, using image-based high content analysis. We show that HD fibroblasts have a distinctive nuclear morphology associated with a nuclear actin cap deficiency. This in turn affects cell motility in a similar manner to fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) patients used as known actin cap deficient cells. Moreover, treatment of the HD cells with either Latrunculin B, used to disrupt actin cap formation, or the antioxidant agent Mitoquinone, used to improve mitochondrial activity, show expected opposite effects on actin cap associated morphological features and cell motility. Deep data analysis allows strong cluster classification within HD cells according to patients’ disease severity score which is distinct from HGPS and matching controls supporting that actin cap is a biomarker in HD patients’ cells correlated with HD severity status that could be modulated by pharmacological agents as tool for personalized drug evaluation.
AB - Primary fibroblasts from patient’s skin biopsies are directly isolated without any alteration in the genome, retaining in culture conditions their endogenous cellular characteristics and biochemical properties. The aim of this study was to identify a distinctive cell phenotype for potential drug evaluation in fibroblasts from Huntington’s Disease (HD) patients, using image-based high content analysis. We show that HD fibroblasts have a distinctive nuclear morphology associated with a nuclear actin cap deficiency. This in turn affects cell motility in a similar manner to fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) patients used as known actin cap deficient cells. Moreover, treatment of the HD cells with either Latrunculin B, used to disrupt actin cap formation, or the antioxidant agent Mitoquinone, used to improve mitochondrial activity, show expected opposite effects on actin cap associated morphological features and cell motility. Deep data analysis allows strong cluster classification within HD cells according to patients’ disease severity score which is distinct from HGPS and matching controls supporting that actin cap is a biomarker in HD patients’ cells correlated with HD severity status that could be modulated by pharmacological agents as tool for personalized drug evaluation.
KW - actin cap
KW - disease marker
KW - huntington’s disease
KW - image-based high content analysis
KW - nuclear morphology
KW - personalized drug screening
KW - primary skin fibroblast
UR - http://www.scopus.com/inward/record.url?scp=85147224722&partnerID=8YFLogxK
U2 - 10.3389/fcell.2023.1013721
DO - 10.3389/fcell.2023.1013721
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C2 - 36743412
AN - SCOPUS:85147224722
SN - 2296-634X
VL - 11
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 1013721
ER -