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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

Led by Sergei Pirogov @biologsp.bsky.social , with key contributions from Artem Ilin @adc34.bsky.social , Aleksander Purik, and collaborators.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

We tested this idea by partially depleting H3K27me3 in the mesoderm, which led to reactivation of genes normally expressed in closely related cell populations.

Epigenetic landscapes for the Krüppel gene locus in wild-type embryos and embryos with a mesoderm-specific knockdown of Polycomb catalytic subunit E(z), which deposits H3K27me3. After knockdown, the repressive "hill" diminishes along the muscle (M) trajectory, and Krüppel is ectopically expressed in muscles.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

In other lineages, these same genes were often silent without H3K27me3 and instead had low promoter accessibility. This suggests that Polycomb repression is especially important when a gene promoter is accessible and exposed to activating inputs.

On the top, epidermal (hindgut) TF byn is expressed and accessible exclusively in the epidermal lineage, and Polycomb-repressed only in the same lineage. However, TF so, expressed at this stage only in muscles, is accessible in all cell types, and repressed everywhere, except muscles. We conclude that Polycomb-mediated repression silences genes with accessible promoters, which probably receive activation cues. When nucleosomes occlude a gene promoter, Polycomb repression is often not necessary.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

Our interpretation is that these genes are active only in specific cell subtypes within that lineage. Polycomb repression likely acts in the other cells of the same lineage, preventing inappropriate activation.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

Many genes were repressed by H3K27me3 only in one cell lineage, and this was often the same lineage in which the gene is normally expressed. How can a gene be both expressed and Polycomb-repressed in the same lineage?

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

Second, lineage-determining transcription factors are repressed in lineages where they are not expressed (as in the case of vvl). But the third pattern was the most unexpected.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

We also revealed that Polycomb does not repress genes in the same way across cell types. First, classical Polycomb targets such as Hox genes are repressed broadly across cell types.

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

We introduce a new way to visualize multidimensional single-cell epigenetic data, including an “epigenetic potential” landscape that combines developmental time, cell type, and antagonistic chromatin marks in a single framework.

We can add the third dimension, which subtracts the active (H3K27ac) signal from the repressive (H3K27me3) signal for a particular gene locus (e.g., epidermal TF vvl). It creates "valleys" permissive for transcription, surrounded by the repressive "hills". The permissiveness increased in the epidermal trajectory, as well as the repressive mark accumulated in endomesodermal trajectories during development. On the right, we project the vvl expression level inferred from the scRNA-seq dataset. Therefore, our visualization can show levels of expression, H3K27-acetylation and -methylation across cell types and along the developmental time

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

We applied nanoCUT&Tag to developing Drosophila embryos at different stages and looked into the distribution of marks across cell types.

On the left, the UMAP visualization of nanoCUT&Tag Drosophila nuclei from 8 to 16 hours of development. On the right, cell-time embedding, where cells are placed according to their developmental cell age (y-axis) and cell lineage (x-axis). We have distinguished five main fly embryo cell types: epidermis, fat body, muscle, midgut and neuronal

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Mannervik Lab @mannerviklab.bsky.social · 02/06/2026

Have you ever wondered how chromatin states shape developmental trajectories? In our preprint, we address this question using single-cell nanoCUT&Tag, a method developed by Marek Bartosovic @mardzix.bsky.social, which simultaneously profiles active H3K27ac and repressive H3K27me3 in the same nucleus

biorxiv.org

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Reposted by Mannervik Lab

The Transmitter @thetransmitter.bsky.social · 13/08/2025

FlyBase, a Drosophila database, will lose a third of its team in early October because the Harvard grant that covered the employees’ salaries was canceled. Scientists warn that losing FlyBase could devastate fly research. By @claudia-lopez.bsky.social www.thetransmitter.org/community/ha...

thetransmitter.org

Harvard University lays off fly database team

The layoffs jeopardize this resource, which has served more than 4,000 labs for about three decades.

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Mannervik Lab @mannerviklab.bsky.social · 18/06/2025

Curious about epigenetics, gene regulation, and developmental biology? Apply for the PhD position in Mannervik lab at Stockholm University! We use single-cell genomics and genetic approaches to uncover how cells acquire their identities during development. Explore the chromatin landscape with us!

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