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Analysis of the Clustered Protocadherin (cPcdh) Locus in Human Pluripotent Stem and Derived Cells

ABSTRACT: Analysis of the Clustered Protocadherin (cPcdh) Locus in Human Pluripotent Stem and Derived Cells

PROVIDER: PRJNA418292 | ENA |

REPOSITORIES: ENA

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Analysis of the Clustered Protocadherin (cPcdh) Locus in Human Pluripotent Stem and Derived Cells

Project description:In the mammalian genome, the clustered protocadherin (cPcdh) locus is a paradigm of stochastic gene expression with the potential to express a different cPcdh combination in every neuron. Here, we report a limited version established during the transition from the naive to the primed states of human cell pluripotency that reduces by orders of magnitude the combinatorial potential in the cPcdh locus. It is a chromatin-based mechanism that increases the frequency of stochastic selection of a subset of cPcdh promoters upon differentiation to fetal-like neurons in monolayers, organoids, or the rat spinal cord. Signs of similar preferential selections can be observed in the brain throughout fetal development, disappearing after birth, but not in a condition of delayed maturation such as Down Syndrome. We therefore propose that pluripotent cells impose a pattern of limited cPcdh diversity on neurons that increases the likelihood of cPcdh repetition until these cells acquire adult-like maturation.

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