Sex chromosomes shape the transcriptional landscape of the preimplantation mouseembryo

Snell, D. M.; Varsally, W.; Courtois, A.; Menchero, S.; Munusamy, P.; Rietdijk, R.; Ojarikre, O. A.; Strohbuecker, S.; Kaya, H.; Sangrithi, M. N.; Turner, J. M.

doi:10.1101/2024.11.26.625424

bioRxiv · 10.1101/2024.11.26.625424

Sex chromosomes shape the transcriptional landscape of the preimplantation mouseembryo

Snell, D. M.·Varsally, W.·Courtois, A.·Menchero, S.·Munusamy, P.·Rietdijk, R.·Ojarikre, O. A.·Strohbuecker, S.·Kaya, H.·Sangrithi, M. N.·Turner, J. M.

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Abstract

Sex chromosomes are emerging as key regulators of adult health and disease in males (XY) and females (XX), but their impact on embryo development is poorly understood. Using single-cell RNA sequencing (scRNA-seq) on wild type and aneuploid mouse embryos, we show that sex chromosomes significantly shape the preimplantation embryo transcriptional landscape. A hierarchy of effects are identified, distinctly mediated by the Y chromosome, the dosage of X chromosomes, X-chromosome imprinting, and by Xist, the non-coding RNA that initiates X-inactivation. The sex chromosomes have strong trans effects on autosomal gene expression throughout preimplantation development. The Y chromosome has an unexpectedly pronounced impact on the trophectoderm, the precursor of the placenta, and this property is shared with genes expressed from the inactive X chromosome. The paternal and maternal X chromosomes differentially promote preimplantation growth, and we identify multiple novel candidate X-linked imprinted genes mediating this effect. Our findings show that sex chromosomes impact the embryo from the beginning of life, long before the appearance of overt sex differences.

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Snell, D. M., Varsally, W., Courtois, A., Menchero, S., Munusamy, P., Rietdijk, R., Ojarikre, O. A., Strohbuecker, S., Kaya, H., Sangrithi, M. N., Turner, J. M.. 2024-11-26. Sex chromosomes shape the transcriptional landscape of the preimplantation mouseembryo. https://doi.org/10.1101/2024.11.26.625424

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