Microenvironment remodeling during human iPSC-derived NSC 3D differentiation

ABSTRACT: Brain microenvironment plays an important role in neurodevelopment and function, where extracellular matrix (ECM) components and soluble factors modulate cellular features, as migration, proliferation survival and neuronal function. Disruption of microenvironment’s homeostasis is often related to pathological conditions. Here, we addressed the microenvironment remodeling occurring during in vitro differentiation of human neural stem cells (NSC) in a three-dimensional (3D) culture system. Proteome and transcriptome dynamics revealed significant changes namely at cell membrane and ECM composition during 3D differentiation, diverging significantly from the profile of monolayer cultures (2D). Structural proteoglycans typically found in brain ECM were enriched during 3D differentiation, while 2D cultures presented increased levels of basement membrane constituents (e.g., laminins, collagens and fibrillins). Moreover, higher expression levels of synaptic machinery and ion transport machinery constituents observed for 3D cultures, both at mRNA and protein levels, suggested a higher degree of neuronal maturation and organization relative to 2D differentiation. This work demonstrated that neural cellular and extracellular features can be recapitulated in the presented 3D neural cell model, highlighting its value to address molecular defects in cell-ECM interactions associated with neurological disorders. Associated GEO dataset is available atGSE102139

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Multipotent Stem Cell, Cell Culture

SUBMITTER: Daniel Simão  

LAB HEAD: Catarina Brito

PROVIDER: PXD007130 | Pride | 2018-07-31

REPOSITORIES: Pride