Advancing Knowledge of Down Syndrome Brain Development and Function With Human Stem Cells

Our bodies are made up of over 250 specific cell types, and all initially arise from stem cells during embryonic development. Stem cells have two characteristics that make them unique: (1) they are pluripotent, meaning that they can differentiate into all cell types of the body, and (2) they are capable of self-renewal to generate more of themselves and are thus able to populate an organism. Human pluripotent stem cells were first isolated from human embryos twenty years ago (Thomson et al., 1998) and more recently, technology to reprogram somatic cells, such as skin and blood, to induced pluripotent stem cells has emerged (Park et al., 2008; Takahashi et al., 2007; Yu et al., 2007). Induced pluripotent stem cells, or iPSCs, are particularly valuable as disease specific iPSCs can be generated from individuals with specific genetic mutations diseases. Researchers have harnessed the power of stem cells to understand many aspects of developmental biology in model organisms (e.g. worms, mice) and more recently, in humans. Human stem cells in culture recapitulate development. For example, formation of the brain occurs prenatally and follows a specific pattern of timing and cell generation. Human stem cells in the culture dish follow a similar pattern when exposed to developmental cues and can thus be used to understand aspects of prenatal human brain development that are not accessible by other means. Disease-specific iPSCs are a valuable tool to model neural development in specific neurodevelopmental disorders like Down syndrome. Down syndrome is a classic developmental disorder; mistakes that are made during development of a particular organ system result in the characteristics of the disorder. In the brain, mistakes during prenatal brain development lead to intellectual disability. Trisomy 21 (Ts21) iPSCs generated from somatic cells of Down syndrome individuals may enable us to understand the mistakes made during Down syndrome brain development.

Characterising the brain metalloproteome in Down syndrome patients with concomitant Alzheimer's pathology

A failure in metal ion homeostasis may be a characteristic feature of the Down syndrome brain.