PREreviews de Dynamic X-chromosomal reactivation enhances female brain resilience

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Dynamic X-chromosomal reactivation enhances female brain resilience

por S Käseberg, M Bertin, R Menon, E Gabassi, H Todorov, S Frank, H Brennenstuhl, B Lohrer, J Winter, J Krummeich, J Winkler, B Winner, E Weis, D Hartwich, S Diederich, K Luck, S Gerber, P Lunt, B Berninger, S Falk, S Schweiger y M Karow

Publicado: 21 de junio de 2023
Servidor: bioRxiv
DOI: 10.1101/2023.06.17.545424

Resumen

Summary

While random X-chromosome inactivation in female cells of placental mammalians silences one allele of the majority of X-chromosomal genes, a considerable fraction is only incompletely and variably inactivated resulting in a tissue-specific pattern of mono- and biallelic expression. Here we used clonal human female induced pluripotent stem cells (iPSCs) allowing to trace the (in)activation status of the two X-chromosomes individually along neural differentiation trajectories. We discovered X-chromosome-wide locus- and lineage-specific dynamic usage of the two X-chromosomal alleles in female cells induced by differentiation. Leveraging iPSCs derived from patients with an X-linked neurodevelopmental disorder, we demonstrate that activation of alleles on the inactive X-chromosome can exert protective effects on the manifestation of disease phenotypes in female neural cells and tissue. Taken together, our data demonstrate that alleles on the inactive X-chromosome can serve as a critical reservoir reactivated during differentiation, thereby enhancing resilience of female neural tissue.

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PREreview de Ryan Cubero y otros/as en ASAPbio Neurobiology Crowd

Redactada por Ryan Cubero, Femi Arogundade, Ana Dorrego-Rivas, Anushree Krishnamurthy y Anna Oliveras en ASAPbio Neurobiology Crowd

This review reflects comments and contributions by Ryan Cubero, Femi Arogundade, Ana Dorrego-Rivas, Anushree Krishnamurthy, Anna Oliveras. Synthesized by Ryan Cubero

In this paper, Käseberg et al. took advantage of the clonal nature and the retention of the X-chromosome activation status in human…

Leer la PREreview de Ryan Cubero et al en ASAPbio Neurobiology Crowd