Vincent Pasque
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pasquelab.bsky.social
Vincent Pasque
@pasquelab.bsky.social
Stem cell and developmental biologist, Professor @ University of Leuven, Belgium. #Pluripotency #Epigenetics
November 25, 2025 at 4:37 PM
This work was a collaborative effort.
A big thanks to all collaborators and funders, in particular: Claire Rougeulle @crougeulle.bsky.social, Jean-François Ouimette @jfouimette.bsky.social
Great contributions from Joost Gribnau, Kathy Niakan @niakanlab.bsky.social, Peter Rugg-Gunn, and others.
November 25, 2025 at 4:37 PM
𝐓𝐡𝐞 𝐢𝐧𝐚𝐜𝐭𝐢𝐯𝐞 𝐗 𝐜𝐡𝐫𝐨𝐦𝐨𝐬𝐨𝐦𝐞 𝐡𝐚𝐬 𝐚𝐧 𝐮𝐧𝐮𝐬𝐮𝐚𝐥 𝐜𝐡𝐫𝐨𝐦𝐚𝐭𝐢𝐧 𝐬𝐭𝐚𝐭𝐮𝐬 𝐢𝐧 𝐡𝐮𝐦𝐚𝐧 𝐞𝐱𝐭𝐫𝐚𝐞𝐦𝐛𝐫𝐲𝐨𝐧𝐢𝐜 𝐜𝐞𝐥𝐥𝐬
Unlike mice, the inactive X chromosome of extraembryonic cells adopts an unusual chromatin landscape, revealing species-specific epigenetic events for the establishment of X inactivation in extraembryonic cells.
November 25, 2025 at 4:37 PM
𝐗𝐈𝐒𝐓 𝐢𝐬 𝐫𝐞𝐪𝐮𝐢𝐫𝐞𝐝 𝐟𝐨𝐫 𝐭𝐡𝐞 𝐞𝐬𝐭𝐚𝐛𝐥𝐢𝐬𝐡𝐦𝐞𝐧𝐭 𝐨𝐟 𝐡𝐮𝐦𝐚𝐧 𝐗-𝐜𝐡𝐫𝐨𝐦𝐨𝐬𝐨𝐦𝐞 𝐢𝐧𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧.
Using the loss of function approach, we show that without XIST, extraembryonic cells fail to establish X-chromosome inactivation, providing the first formal proof that XIST is required for X-chromosome inactivation in humans.
November 25, 2025 at 4:37 PM
The differentiation of naive pluripotent stem cells to two key postimplantation human extraembryonic cell types, extraembryonic mesoderm and trophoblast stem cells, triggers X-chromosome inactivation, robustly recapitulating human X-chromosome inactivation in human extraembryonic cells in vitro.
November 25, 2025 at 4:37 PM
𝐊𝐞𝐲 𝐅𝐢𝐧𝐝𝐢𝐧𝐠𝐬: 𝐍𝐚𝐢𝐯𝐞 𝐡𝐮𝐦𝐚𝐧 𝐩𝐥𝐮𝐫𝐢𝐩𝐨𝐭𝐞𝐧𝐭 𝐬𝐭𝐞𝐦 𝐜𝐞𝐥𝐥𝐬 𝐭𝐨 𝐞𝐱𝐭𝐫𝐚𝐞𝐦𝐛𝐫𝐲𝐨𝐧𝐢𝐜 𝐜𝐞𝐥𝐥 𝐝𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭𝐢𝐚𝐭𝐢𝐨𝐧 𝐢𝐧𝐝𝐮𝐜𝐞𝐬 𝐝𝐞 𝐧𝐨𝐯𝐨 𝐗-𝐜𝐡𝐫𝐨𝐦𝐨𝐬𝐨𝐦𝐞 𝐢𝐧𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐡𝐮𝐦𝐚𝐧𝐬.
November 25, 2025 at 4:37 PM
Yet,
Is XIST required to initiate X-chromosome inactivation in early human extraembryonic lineages?

Is X-chromosome inactivation required for female human embryo development?

𝐎𝐮𝐫 𝐧𝐞𝐰 𝐰𝐨𝐫𝐤 𝐭𝐚𝐤𝐞𝐬 𝐚 𝐦𝐚𝐣𝐨𝐫 𝐬𝐭𝐞𝐩 𝐭𝐨𝐰𝐚𝐫𝐝 𝐬𝐨𝐥𝐯𝐢𝐧𝐠 𝐭𝐡𝐢𝐬 𝐩𝐮𝐳𝐳𝐥𝐞.
November 25, 2025 at 4:37 PM
𝐖𝐡𝐲 𝐝𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐚𝐭𝐭𝐞𝐫?
In mice, X-chromosome dosage compensation is absolutely essential for early female embryo development.

But humans are different!

Recent advances revealed that 𝐭𝐡𝐞 𝐭𝐢𝐦𝐢𝐧𝐠, 𝐝𝐲𝐧𝐚𝐦𝐢𝐜𝐬, 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐦𝐚𝐭𝐢𝐧 𝐟𝐞𝐚𝐭𝐮𝐫𝐞𝐬 𝐨𝐟 𝐗-𝐜𝐡𝐫𝐨𝐦𝐨𝐬𝐨𝐦𝐞 𝐢𝐧𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐡𝐮𝐦𝐚𝐧𝐬 𝐝𝐢𝐟𝐟𝐞𝐫 𝐩𝐫𝐨𝐟𝐨𝐮𝐧𝐝𝐥𝐲 𝐟𝐫𝐨𝐦 𝐦𝐢𝐜𝐞.
November 25, 2025 at 4:37 PM
Thank you, John, for lifting up everyone around you.
October 8, 2025 at 8:40 AM
Congratulations to the Joanna Wysocka lab for their outstanding work that inspired this piece.
#blastoids #stemcells #KULeuven @kuleuvenuniversity.bsky.social
October 1, 2025 at 3:37 PM