TY - JOUR
T1 - Recapitulation of Human Neural Microenvironment Signatures in iPSC-Derived NPC 3D Differentiation
AU - Simão, Daniel
AU - Silva, Marta M.
AU - Terrasso, Ana P.
AU - Arez, Francisca
AU - Sousa, Marcos F.Q.
AU - Mehrjardi, Narges Z.
AU - Šarić, Tomo
AU - Gomes-Alves, Patrícia
AU - Raimundo, Nuno
AU - Alves, Paula M.
AU - Brito, Catarina
N1 - Funding Information:
iNOVA4Health – UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/ Ministério da Educação e Ciência , through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is acknowledged. PD/BD/52473/2014 , PD/BD/52481/2014 , and PD/BD/128371/2017 PhD fellowships funded by FCT , Portugal. N.R. is supported by the European Research Council Starting Grant 337327 . T.S. is supported by a grant provided by the Deutsche Forschungsgemeinschaft (DFG) (grant number SA 1382/7-1 ). The authors gratefully thank João Clemente for support on the bioreactor operation and Dr. Inês Isidro for fruitful discussions on data analysis. MS data were obtained by UniMS – Mass Spectrometry Unit, ITQB/iBET, Oeiras, Portugal.
PY - 2018/8/14
Y1 - 2018/8/14
N2 - Brain microenvironment plays an important role in neurodevelopment and pathology, where the extracellular matrix (ECM) and soluble factors modulate multiple cellular processes. Neural cell culture typically relies on heterologous matrices poorly resembling brain ECM. Here, we employed neurospheroids to address microenvironment remodeling during neural differentiation of human stem cells, without the confounding effects of exogenous matrices. Proteome and transcriptome dynamics revealed significant changes at cell membrane and ECM during 3D differentiation, diverging significantly from the 2D differentiation. Structural proteoglycans typical of brain ECM were enriched during 3D differentiation, in contrast to basement membrane constituents in 2D. Moreover, higher expression of synaptic and ion transport machinery was observed in 3D cultures, suggesting higher neuronal maturation in neurospheroids. This work demonstrates that 3D neural differentiation as neurospheroids promotes the expression of cellular and extracellular features found in neural tissue, highlighting its value to address molecular defects in cell-ECM interactions associated with neurological disorders. In this article, Brito and colleagues show that differentiation of human neural stem cells as three-dimensional neurospheroids induces significant changes at cell membrane and ECM composition, relative to monolayer cultures, mimicking a neural-like microenvironment. These findings support the potential of neurospheroids to address ECM-affecting neurological disorders.
AB - Brain microenvironment plays an important role in neurodevelopment and pathology, where the extracellular matrix (ECM) and soluble factors modulate multiple cellular processes. Neural cell culture typically relies on heterologous matrices poorly resembling brain ECM. Here, we employed neurospheroids to address microenvironment remodeling during neural differentiation of human stem cells, without the confounding effects of exogenous matrices. Proteome and transcriptome dynamics revealed significant changes at cell membrane and ECM during 3D differentiation, diverging significantly from the 2D differentiation. Structural proteoglycans typical of brain ECM were enriched during 3D differentiation, in contrast to basement membrane constituents in 2D. Moreover, higher expression of synaptic and ion transport machinery was observed in 3D cultures, suggesting higher neuronal maturation in neurospheroids. This work demonstrates that 3D neural differentiation as neurospheroids promotes the expression of cellular and extracellular features found in neural tissue, highlighting its value to address molecular defects in cell-ECM interactions associated with neurological disorders. In this article, Brito and colleagues show that differentiation of human neural stem cells as three-dimensional neurospheroids induces significant changes at cell membrane and ECM composition, relative to monolayer cultures, mimicking a neural-like microenvironment. These findings support the potential of neurospheroids to address ECM-affecting neurological disorders.
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U2 - 10.1016/j.stemcr.2018.06.020
DO - 10.1016/j.stemcr.2018.06.020
M3 - Article
C2 - 30057262
AN - SCOPUS:85053846000
VL - 11
SP - 552
EP - 564
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 2
ER -