A Computational Approach to Investigate TDP-43 RNA-Recognition Motif 2 C-Terminal Fragments Aggregation in Amyotrophic Lateral Sclerosis.

Many of the molecular mechanisms underlying the pathological aggregation of proteins observed in neurodegenerative diseases are still not fully understood. Among the aggregate-associated diseases, Amyotrophic Lateral Sclerosis (ALS) is of relevant importance. In fact, although understanding the processes that cause the disease is still an open challenge, its relationship with protein aggregation is widely known.

Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs.

Fragile X syndrome (FXS) is a neurodevelopmental disorder, characterized by intellectual disability and sensory deficits, caused by epigenetic silencing of the FMR1 gene and subsequent loss of its protein product, fragile X mental retardation protein (FMRP). Delays in synaptic and neuronal development in the cortex have been reported in FXS mouse models; however, the main goal of translating lab research into pharmacological treatments in clinical trials has been so far largely unsuccessful, leaving FXS a still incurable disease. Here, we generated 2D and 3D in vitro human FXS model systems based on isogenic FMR1 knock-out mutant and wild-type human induced pluripotent stem cell (hiPSC) lines.

A pre-existing population of ZEB2 quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer.

Background: Quiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown.

Methods: A population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses.

3D Bioprinted Human Cortical Neural Constructs Derived from Induced Pluripotent Stem Cells.

Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner and with micrometric resolution. 3D bioprinted structures representative of several human tissues have been recently produced using cells derived by differentiation of induced pluripotent stem cells (iPSCs). Human iPSCs can be differentiated in a wide range of neurons and glia, providing an ideal tool for modeling the human nervous system.

Inducible SMARCAL1 knockdown in iPSC reveals a link between replication stress and altered expression of master differentiation genes.

Schimke immuno-osseous dysplasia is an autosomal recessive genetic osteochondrodysplasia characterized by dysmorphism, spondyloepiphyseal dysplasia, nephrotic syndrome and frequently T cell immunodeficiency. Several hypotheses have been proposed to explain the pathophysiology of the disease; however, the mechanism by which mutations cause the syndrome is elusive. Here, we generated a conditional SMARCAL1 knockdown model in induced pluripotent stem cells (iPSCs) to mimic conditions associated with the severe form the disease.

Construction of 3D in vitro models by bioprinting human pluripotent stem cells: Challenges and opportunities.

Three-dimensional (3D) printing of biological material, or 3D bioprinting, is a rapidly expanding field with interesting applications in tissue engineering and regenerative medicine. Bioprinters use cells and biocompatible materials as an ink (bioink) to build 3D structures representative of organs and tissues, in a controlled manner and with micrometric resolution. Human embryonic (hESCs) and induced (hiPSCs) pluripotent stem cells are ideally able to provide all cell types found in the human body.