Actin cytoskeleton dynamics in stem cells from autistic individuals

Author(s):Show less -

Griesi-Oliveira, Karina ^{[1, 2]} ; Suzuki, Angela May ^[2] ; Alves, Aline Yasuda ^[1] ; Cintra Nunes Mafra, Ana Carolina ^[1] ; Yamamoto, Guilherme Lopes ^[2] ; Ezquina, Suzana ^[2] ; Magalhaes, Yuli Thamires ^[3] ; Forti, Fabio Luis ^[3] ; Sertie, Andrea Laurato ^[1] ; Zachi, Elaine Cristina ^[4] ; Vadasz, Estevao ^[5] ; Passos-Bueno, Maria Rita ^[2]

Affiliation

^[1] Hosp Israelita Albert Einstein, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biociencia, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Psicol, Dept Psicol Expt, Nucleo Neurociencias & Comportamento, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Psiquiatria, Fac Med, Hosp Clin, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JUL 24 2018.
• Web of Science Citations: 1

Abstract

Several lines of indirect evidence, such as mutations or dysregulated expression of genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics is functionally altered in cells from ASD patients. Here we investigated the regulation of actin cytoskeleton dynamics in stem cells from human exfoliated deciduous teeth (SHEDs) of 13 ASD patients and 8 control individuals by inducing actin filament depolymerization and then measuing their reconstruction upon activation of the RhoGTPases Rac, Cdc42 or RhoA. We observed that stem cells from seven ASD individuals (53%) presented altered dymanics of filament reconstruction, including a patient recently studied by our group whose iPSC-derived neuronal cells show shorten and less arborized neurites. We also report potentially pathogenic genetic variants that might be related to the alterations in actin repolymerization dynamics observed in some patient-derived cells. Our results suggest that, at least for a subgroup of ASD patients, the dynamics of actin polymerization is impaired, which might be ultimately leading to neuronal abnormalities. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC