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Chunk #9 — Main Text — Defining Cell States

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Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders.
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Ronald McKay, of the Lieber Institute for Brain Studies, further considered molecular regulation of stem cell identity. Sophisticated immunohistochemical analyses revealed unexpected dynamics in the level of pluripotent gene expression, which was high immediately following passaging and declined between splitting and varied between colonies and cultures, relative to their location within the colony (Chen et al., 2014). The transcriptional identity of each stem cell line, however, was stable across datasets and between laboratories, evidence that the dynamic variation between PSCs is defined by our individual human genomes (Adamo et al., 2015). This transcriptional identity not only is conserved in replicate cell lines derived from the same genome but also is stable throughout differentiation; the signature can be detected in post-mortem brain tissue matched to individual stem cell lines. Such signatures may provide a useful means to both classify and assess risk within stratified patient populations without requiring advance knowledge of the target neural cell type(s).