I am thrilled to share our preprint where we take advantage of the unique opportunities offered by human blastoids to uncover a human-specific mechanism potentially playing a role in preimplantation 🧵. www.biorxiv.org/content/10.1... - ThreadSky

fueyoraquel.bsky.social • 15 days ago

I am thrilled to share our preprint where we take advantage of the unique opportunities offered by human blastoids to uncover a human-specific mechanism potentially playing a role in preimplantation 🧵. https://www.biorxiv.org/content/10.1101/2025.05.10.653263v1

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julianeg.bsky.social•15 days ago

Congratulations Raquel!!! Great to see it out and so looking forward to reading it in details!

fueyoraquel.bsky.social•15 days ago

Thanks @julianeg.bsky.social !

fueyoraquel.bsky.social•15 days ago

In this work, we investigate a longstanding question in genome biology: Do endogenous retroviruses (ERVs) play a role in human embryogenesis? Spoiler alert, at least in this 3D model, they do!

fueyoraquel.bsky.social•15 days ago

To answer this question, we used as a model the youngest ERV in our genome: HERVK LTR5Hs. HERVK LTR5Hs is active from the 8-cell stage, and it peaks in the blastocyst. It invaded the genome in hominoids, but some insertions are specific to humans and even polymorphic in the population.

fueyoraquel.bsky.social•15 days ago

We repressed HERVK LTR5Hs en masse using CARGO LTR5Hs. This revealed that LTR5Hs activity affects the blastoid-forming potential in a dose-dependent manner. We analyzed > 20 clones for each condition (equivalent to ~140 K human blastoids! Close to the population of my hometown León…😂)

fueyoraquel.bsky.social•15 days ago

Near-full LTR5Hs repression is incompatible with blastoid formation, but can we take advantage of the medium repression clones to study the impact of HERVK LTR5Hs on lineage determination? Yes!

fueyoraquel.bsky.social•15 days ago

Using IFs and scRNA-seq we demonstrate that LTR5Hs repression drives gene expression changes in the blastoids epiblast. Comparisons with human embryo data suggest these changes represent a defect in maturation. In agreement, we also detected a reduction of hypoblast cells.

fueyoraquel.bsky.social•15 days ago

Remarkably, comparison between the genes regulated by LTR5Hs in blastoids and the genes expressed in the mouse epiblast reveals that the HERVK invasion diversified the epiblast transcriptome in humans.

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