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Posts by Dorien Pastoors

Dankjewel!

3 days ago 1 0 0 0

Thank you Emilie!!

3 days ago 1 0 0 0
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Thirteen early-career researchers set to cross borders thanks to Rubicon grants | NWO No fewer than thirteen talented researchers who have recently completed their PhDs are being given the opportunity to gain valuable research experience abroad. The Rubicon round, organised by NWO, had...

I am very happy to have been awarded a Rubicon Postdoctoral fellowship from the NWO (Dutch Science Council) (Science/Life Sciences domain) for my postdoc in the @tothovalab.bsky.social at @danafarber.bsky.social / @broadinstitute.org!
www.nwo.nl/en/news/thir...

4 days ago 5 1 2 0
A dual role for CTCF in development CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 637587, 865459 Dutch Research Council, https://ror.org/04jsz6e67, 016.161.316, VI.C.222.049 Dutch Cancer Society, https://ror.org/0368jnd28, N/A

🧡 CTCF is essential for embryonic development, but why has remained unclear. By combining gastruloids with a temporal degron system, we uncovered a surprising dual function β€” and it changes how we think about CTCF's role in development. 1/8 www.biorxiv.org/content/10.6...

1 month ago 112 55 7 4

wow! thanks for sharing! this looks so useful!

1 month ago 2 0 0 0

Yes!! In september. Im now in the lab of zuzana tothova. I know... it was a revelation such a community existed though

2 months ago 1 0 0 0

@timtriche.bsky.social @paralkarlab.bsky.social the blood-themed valentine cards remind me a little of our initial struggles with trying to get out of the vampire vibes VS hematology community by using bloodsky instead of hemesky... Haha

2 months ago 1 0 1 0
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having a look at my HemeSky feed for the first time in a while (have been on an off bluesky a bit) but this looks so interesting!
my HemeSky feed picks up interesting papers as well podcasts such as this one, and also blood-themed valentine cards πŸ‘€ (@ash.hematology.org ) :
bsky.app/profile/dpas...

2 months ago 3 0 2 0

Woww 🀯🀯 mind blown on saturday morning!! Must-read thread ⬇️

2 months ago 2 0 0 0

Haha yes it is - we were concerned about this being an issue but we had beautiful signal even though we used the blue laser. It smells a bit different as well πŸ€” more floral or sweeter than dreft I think

3 months ago 2 0 0 0

Preprint alert: Jiangyuan Liu developed a new workflow for chromatin loop calling across Hi-C datasets, e.g., during differentiation. Most loops are shared between datasets/cell states. Important work for all interested in chromatin loops and how to identify them!

www.biorxiv.org/content/10.6...

3 months ago 26 16 0 0

Rotation PhD student @emiliedevet.bsky.social in our lab made the Dish soap protocol work (on the first attempt) for a nuclear target with Dawn (the US version of dreft/fairy ) and thereby extended the dish soap protocol to a version for across the atlantic 🀩 @tothovalab.bsky.social #hemesky

3 months ago 12 5 0 2
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Progress and challenges in profiling protein-RNA and protein-associated RNA-RNA interactions - PubMed RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-R …

Happy to share Joey (Zhuoyi)'s review on technologies to map RBP:RNA and (especially) RBP-associated RNA:RNA interactions is now up at RNA! pubmed.ncbi.nlm.nih.gov/41535089

3 months ago 24 8 1 2

We are very intrigued - @emiliedevet.bsky.social is going to give Dawn a try this week! (The US version of fairy/dreft)

3 months ago 2 0 0 0

Thank you!

3 months ago 0 0 0 0
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@bloodgenes.bsky.social I wanted to wait until the physical copy, sorry for my late reply haha

3 months ago 1 0 0 0

Thanks Vijay!! Congratulations to your manuscript too - really cool to see that it's out!

3 months ago 1 0 1 0
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This was the first time I got to hold my own physical article this morning!! Very exciting

3 months ago 3 0 1 0
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CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias Key PointsMECOM promotes malignant stem cell–like states in aggressive AMLs by directly repressing prodifferentiation gene regulatory programs.A MECOM-boun

Thanks to all the co-authors - @delwelruud.bsky.social ! This paper was accompanied by a paper from @tjflemin.bsky.social and @bloodgenes.bsky.social with similar conclusions and very cool dCas9 experiments: ashpublications.org/blood/articl...

3 months ago 2 0 1 0

In this paper we show how dose-control of CEBPA is essential to maintain the phenotype of MECOM-rearranged AML. Notably, differentiation by MECOM degradation is able to switch of the enhancers driving MECOM expression over time. However, we don't know if differentiation alone will do the same.

3 months ago 0 0 1 0
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In patient samples, CEBPA is reduced in patients that express MECOM through a 3q26-rearrangment or unknown mechanism of overexpression.

3 months ago 0 0 1 0
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The upregulation of CEBPA is partially CTBP1/2 dependent, as overexpression of our earlier MECOM/CTBP interfering peptide PLDLS also increases CEBPA levels (but not the negative control PLASS).

3 months ago 0 0 1 0
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Only upon MECOM depletion, the enhancer becomes truly active to upregulate CEBPA. This also leads to the appearance of a CEBPA footprint in ATAC-signal.

3 months ago 0 0 1 0
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MECOM regulates CEBPA through binding to its +42kb enhancer; an enhancer that is bound by many TFs at baseline in our cells despite being largely inactive (in fact, it had been our positive control in ChIP-seq because of this).

3 months ago 0 0 1 0
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We show that CEBPA is among the first genes to be upregulated upon acute MECOM loss.

3 months ago 0 0 1 0
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Although this is a seemingly simple mechanism as noted in the commentary, it took a long time to find CEBPA as a target because of the huge effect MECOM on differentiation status. We solved this by using a degron model.

3 months ago 0 0 1 0
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How do single transcription factors prevent lineage differentiation?
In this issue of Blood, the second paper of my PhD is published. We show that MECOM, a key HSC TF, maintains stem cell state by preventing change through repression of CEBPA. #hemesky ashpublications.org/blood/articl...

3 months ago 6 1 1 0

For our #flowcytometry peeps, would you like to have a single fix/perm protocol that is optimised for everything? One that preserves fluorophores while allowing simultaneous TF and cytokine staining? How about 100-fold cheaper?

You got it:
currentprotocols.onlinelibrary.wiley.com/doi/10.1002/...

7 months ago 160 70 10 11

Thanks cansu!!

7 months ago 0 0 0 0
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Excited to share that I started as a Postdoctoral Fellow in @tothovalab.bsky.social at @danafarber.bsky.social in Boston! Looking forward to the next years of molecular & myeloid biology in Boston πŸ€©πŸŒ‡

7 months ago 32 1 4 0