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Chunk #7 — Understanding neuropsychiatric disease — Induced pluripotent stem cells: development backward

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Pluripotent stem cells in neuropsychiatric disorders.
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In 1998, Thomson et al.18 first established the technique of isolating human embryonic stem cells (hESCs) from blastocysts. When cultured, these cells can be maintained in an undifferentiated, pluripotent state indefinitely, enabling researchers to generate an unlimited number of cells. Furthermore, hESCs are pluripotent and thus can differentiate into any human tissue, including neurons and glia when guided through the appropriate developmental pathways. This is traditionally achieved through exposing hESCs to a combination of growth factors and modulators of specific signaling pathways. These protocols can generate progenitor cell types along the developmental spectrum and adult-like cell types of varying maturity.19 Hence, hESCs opened the door to investigating early human development and understanding molecular mechanisms driving cellular differentiation. However, the need to harvest these cells from human embryos generated considerable ethical controversy. This was resolved by the Nobel prize-winning discovery that adult somatic cells can be reprogrammed into cells with embryonic stem cell properties by the introduction of as few as four specific transcription factors.20 These cells were termed induced pluripotent stem cells (iPSCs).