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1.
Nat Cell Biol ; 24(6): 981-995, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35697781

RESUMO

Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early Dual SMAD and WNT inhibition course is necessary and sufficient to establish robust and lasting cortical organoid NSC identity, efficiently suppressing non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC-specification capacity. Accordingly, this method selectively enriches for outer radial glia NSCs, which cyto-architecturally demarcate well-defined outer sub-ventricular-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD and WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring of fundamental molecular and cyto-architectural features of cortical development and meaningful disease modelling.


Assuntos
Células-Tronco Neurais , Organoides , Diferenciação Celular , Córtex Cerebral , Células Ependimogliais , Humanos , Neurogênese , Neurônios
2.
Materials (Basel) ; 12(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146402

RESUMO

Here we explore the structural properties and damage sensing of cementitious mortars after a freeze-thaw process (F-T) as a function of nano-modification. For this purpose, carbon nanotubes were added at 0.2-0.8 wt.% cement using two different dispersive agents. F-T resulted in reduced fracture energy in nano-modified specimens prepared using superplasticizer as a dispersant while the opposite held true for the surfactant-containing ones. All nano-modified mortars possessed significantly higher fracture energy compared to the plain specimens after F-T (up to 73% improvement). The acoustic emission activity was lower after F-T, while acoustic emission indicators revealed a more tensile mode of fracture in both plain and nano-modified mortars.

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