iiinova — where your digital self keeps evolving

Huge thanks to the whole team behind this work @crick.ac.uk and collaborators at @riken-bdr.bsky.social and the University of Texas Rio Grande Valley

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Our work reveals stage-specific roles of RSX in marsupial X-inactivation and highlights the remarkable evolutionary flexibility in dosage compensation mechanisms, in which RSX and Xist can drive X-inactivation despite exhibiting no primary sequence homology

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Interestingly, H2AK119ub was not enriched on the opossum inactive X, indicating divergence in recruitment of repressive marks between eutherians and marsupials

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RSX deletion in opossum fibroblasts, when X-inactivation is already established, only causes modest X-gene de-repression, with repressive chromatin marks H3K27me3 and H3K9me3 retained

A control and an RSX KO female opossum fibroblast cell are shown. In both cases, only one dot representing MSN (an X-linked gene) expression is seen in each cell. On the right panel, the percentage of reads from the maternal and paternal allele for 6 genes is shown for control and RSX KO cells

It took time but we set up zygote microinjection in opossums to knock out RSX and found that RSX is required for the initiation of X-inactivation in embryos. X-linked genes were expressed from both Xs in the opossum embryo upon RSX deletion

This image shows an unedited embryonic cell from an opossum with RSX in magenta and an X-linked gene (MSN) in green. Below, an RSX-edited cell shows no RSX signal but instead two MSN signals, corresponding to both X chromosomes. On the right panel, a graph represents percentage of reads from maternal and paternal alleles for 6 X-linked genes

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Xist mediates X-inactivation in eutherians but is absent from marsupials. In 2012, we found RSX, an evolutionarily unrelated X-linked lncRNA with silencing capabilities expressed in female marsupial cells. It was a great candidate, but genome editing in opossums was not easy 🧬

Turner Lab @lab-turner.bsky.social · 19/05/2026

2026 Mammalian Reproduction GRC reminder: Deadline for abstract submission for oral presentation is June 1st, don't miss it!

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Turner Lab @lab-turner.bsky.social · 21/04/2026

Join us at the Mammalian Reproduction GRC conference next August in Maine! We have a fantastic line of speakers and free slots for talks selected from abstracts. Don't miss it! www.grc.org/mammalian-re...

grc.org

2026 Mammalian Reproduction Conference GRC

The 2026 Gordon Research Conference on Mammalian Reproduction will be held in Newry, Maine. Apply today to reserve your spot.

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Turner Lab @lab-turner.bsky.social · 23/10/2025

This work was led by Ruta Meleckyte and Waz Varsally, with Ben Powell, Jasmin Zohren, and in collaboration with @astra-zeneca.bsky.social

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Turner Lab @lab-turner.bsky.social · 23/10/2025

Our latest 📢 We generated isogenic iPSCs with XX, XY, XO and XXY karyotypes to study sex chromosome effects 🧫 While XX and XY transcriptomes are similar, XO cells showed an important effect of the Y and inactive X @crick.ac.uk @stemcellreports.bsky.social www.sciencedirect.com/science/arti...

sciencedirect.com

A human induced pluripotent stem cell toolbox for studying sex chromosome effects

Sex chromosomes shape male (XY)-female (XX) differences in development and disease. These differences can be modeled in vitro by comparing XY and XX h…

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Turner Lab @lab-turner.bsky.social · 25/07/2025

Paper alert! 🚨 Something new from us, and this time it's not sex chromosome related 😱 All led by @sermenchero.bsky.social who used the opossum as a model to understand developmental heterochrony. Transcriptional and morphological progression of dev programs are decoupled www.cell.com/developmenta...

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Reposted by Turner Lab

Jamie Hackett @jamiehackett.bsky.social · 15/05/2025

We are looking to take on an intern at EMBL Rome, for anyone interested in CRISPR and Epigenetics training. The traineeship is 3-12-months, in Rome (Italy), should start by July, and is supervised by the outstanding @steliostsagkris.bsky.social. #job #internship; see info below...

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This project was a massive team effort, within our lab, with collaborators, and with help from @crick.ac.uk facilities @sermenchero.bsky.social @aureliencourtois.bsky.social and others not on Bluesky

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In marsupials, X inactivation is imprinted, affecting the paternally-inherited X chromosome, and is thought to be regulated by the non-coding RNA RSX. When comparing sperm and oocytes at the RSX locus, we see a differentially methylated region, which might be a regulatory mechanism for imprinted XCI

Of course, we also dig into epigenetic regulation of X chromosome inactivation. The inactive X in adult marsupial cells adopts an unusual hypomethylated state – devoid of DNA methylation. Using our embryo data we show that the inactive X progressively loses methylation throughout early development

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Our study suggests that a unique extra-embryonic methylation state is a conserved feature of mammals – and therefore is likely to be important for the evolution of the placenta

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Secondly, after 5 days, DNA methylation drops, but does so largely in the extra-embryonic trophectoderm cells that will go to form the placenta, while remaining largely unchanged in the cells that give rise to the embryo proper

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The paper provides two main important findings. Firstly, in contrast to mouse, early wiping of DNA methylation simply doesn’t happen in the marsupial embryos (up to day 5), with methylation levels remaining consistent during embryo genome activation and pluripotent stem cell formation

To address this question, we looked at the DNA methylation of marsupial embryos, which split from eutherian mammals 160 million years ago. By leveraging the more spaced out embryo development in marsupials we mapped changes in the epigenome to the processes described above

In eutherian (placental) mammals, the early embryo “wipes” its epigenome, but we don't know why. Many things happen early in placental mammalian embryos, and all in very quick succession: the embryo genome activates, pluripotent stem cells appear, and the placental precursor cells are formed

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Divergent DNA methylation dynamics in marsupial and eutherian embryos - Nature

We're excited to publish our latest study led by Bryony Leeke @bryonyleeke.bsky.social and Wazeer Varsally, now out in @nature.com 🍾This study focusses on the epigenome of marsupial embryos 🦘 mapping DNA methylation in embryo development to specific embryo events www.nature.com/articles/s41... 🧵

nature.com

A study reports on the DNA methylation dynamics during embryogenesis in marsupials, showing that these differ from those occurring during embryogenesis in eutherian mammals.

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Turner Lab @lab-turner.bsky.social · 07/03/2025

These well-defined cell lines provide a unique platform to investigate the role of sex as a biological variable across diverse cell types and to elucidate the impact of sex chromosome complement in human disease models 🧫🧬

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Turner Lab @lab-turner.bsky.social · 07/03/2025

We are excited to share our latest preprint led by Ruta Meleckyte and Waz Varsally! www.biorxiv.org/content/10.1... We generated a set of human isogenic induced pluripotent stem cells (hiPSCs) that are autosomally identical but differ in sex chromosome composition: XX, XY or monosomic X

biorxiv.org

A human induced pluripotent stem cell toolbox for studying sex chromosome effects

Sex chromosomes shape male (XY) - female (XX) differences in development and disease. These differences can be modelled in vitro by comparing XY and XX human induced pluripotent stem cells (hiPSCs). H...

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Reposted by Turner Lab

Young Embryologist Network @yen-network.bsky.social · 30/01/2025

Registration and abstract submission for YEN 2025 is officially open! We are looking forward to seeing you at the 17th Young Embryologist Network Conference on the 19th May 2025. Attendence is FREE thanks to our amazing sponsors: @biologists.bsky.social @10xgenomics.bsky.social and Azenta.

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This work was only possible because of the amazing facilities at @crick.ac.uk and our wonderful collaborators.

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We generate a bulk and single nuclei RNAseq atlas of Y-gene KOs, identifying possible underlying molecular mechanisms causing spermatogenic defects. We see an interesting impact of Y genes on somatic cells of the testis

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We make the equivalent of the human infertility AZFa deletion encompassing Uty, Ddx3y and Usp9y. We reveal phenotypes absent in single KOs, uncovering a detrimental cumulative effect of Y-gene loss on spermatogenesis.

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The transcription activator Zfy2 promotes meiotic pairing and reciprocal recombination between the sex chromosomes.

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We found that the histone demethylase Uty functions early in spermatogenesis, regulating the establishment of the spermatogonial stem cell pool and the later spermatogonial differentiation.

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While some Y genes are dispensable, others are key for mouse spermatogenesis. We find novel functions for Y genes in spermatogonial, meiotic, post-meiotic and somatic cells.

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Great summary of our latest paper studying the role of Y genes in spermatogenesis. ⬇️

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