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Johannes Stein

@jmstein.bsky.social

1.2K followers 570 following 38 posts

Studying genome organization with quantitative super-resolution microscopy | Postdoc at Harvard/Wyss | PhD at MPIB and LMU https://www.researchgate.net/profile/Johannes-Stein-4

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Johannes Stein @jmstein.bsky.social · Aug 13

(1/n) DNA-PAINT imaging inside the nucleus at single antibody resolution using TIRF? Ultrathin sectioning makes it happen!

Grateful to share my postdoctoral work introducing “tomographic & kinetically-enhanced DNA-PAINT” or in brief: tkPAINT. Out in @pnas.org!
doi.org/10.1073/pnas...
👇🧵

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Reposted by Johannes Stein

Edda Schulz @eddaschulz.bsky.social · 2d

⚠️ Paper alert: Using a novel CRISPR screening approach, we mapped the entire regulatory network controlling Xist—key for X-chromosome inactivation.
👉 We discover how sex and development signals are decoded at a single gene locus.
www.nature.com/articles/s41...
👇 Bluetorial

Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus - Nature Structural & Molecular Biology

Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

www.nature.com

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Reposted by Johannes Stein

Raquel Fueyo @fueyoraquel.bsky.social · 6d

Today in @nature.com, we present our work leveraging functional genomics and human blastoids to uncover a human-specific mechanism in preimplantation development driven by the endogenous retrovirus HERVK.
Special thanks to the reviewers whose comments improved our manuscript a lot! rdcu.be/eI3tD

A human-specific regulatory mechanism revealed in a pre-implantation model

Nature - Genetic manipulation of blastoids reveals the role of recently emerged transposable elements and genes in human development.

rdcu.be

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Reposted by Johannes Stein

JungmannLab @jungmannlab.bsky.social · 6d

Highly efficient 12-color multiplexing with speed-optimized DNA-PAINT. We are excited to share our latest paper in @natcomms.nature.com, using left-handed DNA to extend speed-optimized DNA-PAINT to 12 targets in a simple and straightforward way! 🧬👈🚀https://www.nature.com/articles/s41467-025-64228-x

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Reposted by Johannes Stein

Bas van Steensel lab (NKI) @basvansteensellab.bsky.social · 14d

Our reporter hopping scaled up to thousands of integrations in a single locus, to produce high-resolution functional maps, with plenty of interesting insights: www.science.org/doi/10.1126/...

Functional maps of a genomic locus reveal confinement of an enhancer by its target gene

Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt...

www.science.org

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Reposted by Johannes Stein

Dr. Sedona Murphy @sedonamurphy.bsky.social · 19d

Congrats to my friends in the Boettiger lab for this really beautiful live imaging work. A big leap forward in understanding the dynamic side of genome organization. www.science.org/doi/10.1126/...

Kinetic organization of the genome revealed by ultraresolution multiscale live imaging

Genome function requires regulated genome motion. However, tools to directly observe this motion in vivo have been limited in coverage and resolution. Here we introduce an approach to tile mammalian c...

www.science.org

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Reposted by Johannes Stein

Christophe 🔬 L @christlet.bsky.social · 20d

Our new preprint is up! This is the main postdoc work of @wiesner-t.bsky.social focusing on exocytosis along the axon shaft and its regulation by the sub membrane actin-spectrin scaffold: www.biorxiv.org/content/10.1...
Read the thread below for a summary of our findings 🧵1/11

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Reposted by Johannes Stein

Carmelo Ferrai @carmeloferrai.bsky.social · May 13

EpiSci - Hi there! Our review “Mechanotransduction in stem cells” is finally published. With @carstenschulte4.bsky.social we provided a comprehensive picture, that aims to cover the whole mechanotransductive pathway from the cell microenvironment to the nucleus. 1/3 pubmed.ncbi.nlm.nih.gov/38729084/

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Reposted by Johannes Stein

Heilemann Lab @heilemannlab.bsky.social · Aug 29

And we are done --- #SMLMS2025 is over, and it was great. Thank you Uli & Ulrike & all the helpers 👍, and thanks to everyone joining this event 🙏 ... safe travels home & see you soon!

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Reposted by Johannes Stein

André Nadler @nadlerlab.bsky.social · Aug 21

Out today in @nature.com: Together with the Honigmann, Shevchenko, Drobot and Hof labs, we present a general workflow for imaging the localization and transport of individual lipids in cells and mapping their metabolism.
www.nature.com/articles/s41...

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Reposted by Johannes Stein

Laura Breimann @laurabreimann.bsky.social · Aug 16

Excited that our paper was published in Science Advances 🧪
Great work by first author Merrick Pierson Smela who will carry this work forward in his new start-up!

The Wyss Institute at Harvard University @wyssinstitute.bsky.social · Aug 15

Wyss researchers have induced human stem cells to initiate meiosis – a key step in creating eggs and sperm – in the lab for the first time. This work was published in @science.org Advances.

Recapitulating egg and sperm development in the dish

By Benjamin Boettner (BOSTON) — More than one-sixth of adults around the world experience infertility in their lifetime. There is a high unmet need not only for increased access to affordable, high-q...

wyss.harvard.edu

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Reposted by Johannes Stein

Sven Klumpe @svenklumpe.bsky.social · Aug 15

Extremely excited for the second version of this workshop at the MPI of Biophysics l, Frankfurt, that will happen 12-20. April 2026. Absolutely amazing lineup of speakers, I am very much looking forward to learning from everyone! Apply here: meetings.embo.org/event/26-in-...

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Reposted by Johannes Stein

Eric Joyce @ericjoyce.bsky.social · Aug 14

🚨New preprint from the lab🚨
🧬 What keeps certain chromatin domains anchored at the nuclear periphery? Our new genome-wide HiDRO screen uncovers a key role for RNA-binding protein hnRNPK.
www.biorxiv.org/content/10.1...

Mechanistic and Epigenetic Partitioning of Lamina-Associated Chromatin Revealed by a Genome-Wide Imaging Screen

The nuclear periphery is a key site for heterochromatin organization in eukaryotic cells, where lamina-associated domains (LADs) promote transcriptional repression and genome stability. Despite their ...

www.biorxiv.org

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Johannes Stein @jmstein.bsky.social · Aug 14

Thank you, Anush!

Johannes Stein @jmstein.bsky.social · Aug 13

(16/n) Last but not least, massive thanks also to the many colleagues and experts whose support and advice helped make this project a success – and most importantly – great fun🙏!!!

Johannes Stein @jmstein.bsky.social · Aug 13

(15/n) @humboldtuni.bsky.social @biovitenskap.bsky.social @laurabreimann.bsky.social as well as @embo.org for fellowship funding! And once again, to my outstanding PhD mentors Petra Schwille and @jungmannlab.bsky.social with whom my journey into microscopy and DNA-PAINT started🙏!

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Johannes Stein @jmstein.bsky.social · Aug 13

(14/n) Huge thanks to everyone involved in this team effort, my incredible postdoc mentors @tingwu-lab.bsky.social & @geochurch.bsky.social, the @apombo1.bsky.social lab‬ @mdc-berlin.bsky.social for a fantastic collaboration, all co-authors at @wyssinstitute.bsky.social @harvardmed.bsky.social🙏

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Johannes Stein @jmstein.bsky.social · Aug 13

(13/n) To conclude, we believe tkPAINT will be a valuable addition to the toolbox of DNA-PAINT 🔬🧬✨, strengthening its potential for spatial biology across diverse sample types, leveraging ultrastructural preservation and unlocking an interface to correlative electron microscopy.

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Johannes Stein @jmstein.bsky.social · Aug 13

(12/n) tkPAINT will greatly complement whole cell DNA-PAINT imaging and in case you have missed recent advances on that front, you should check out the fantastic work e.g. by the @gustavssonlab.bsky.social and Simoncelli labs.
www.nature.com/articles/s41...
www.nature.com/articles/s41...

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Johannes Stein @jmstein.bsky.social · Aug 13

(11/n) Not interested in nuclear biology? No problem! Decades of Tokuyasu Immunogold EM/CLEM/LM protocols optimized for all kingdoms of life 🐀🦠🌾🍄 will provide immediate starting points for your tkPAINT experiment – team up with your local EM experts!

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Johannes Stein @jmstein.bsky.social · Aug 13

(10/n) Using a simple custom-addition to our TIRF scope (700$, described in SI), we finally map nuclear antigens via 3D tkPAINT imaging based on astigmatism.

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Johannes Stein @jmstein.bsky.social · Aug 13

(9/n) Multiplexing and multimodal imaging? Yes.
Nuclear tkPAINT works seamlessly with Exchange-PAINT and earlier multimodal cryosection protocols targeting proteins, nucleic acids, or both🔄🧬.

Johannes Stein @jmstein.bsky.social · Aug 13

(8/n) Physical sectioning = no detergent needed🫧❌.
tkPAINT allows imaging throughout ultrastructurally-preserved cells without permeabilization → detergent-sensitive antigens are retained.
Sections are thus also promising samples for structural fluorescence imaging methods like MINFLUX & RESI.

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Johannes Stein @jmstein.bsky.social · Aug 13

(7/n) tkPAINT opens the door for spatial biology studies in both cultured cells & tissues at identical resolution – revealing, for instance, cell- and tissue-specific Pol II heterogeneities.

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Johannes Stein @jmstein.bsky.social · Aug 13

(6/n) …and favor molecular counting in the nucleus📊!
With qPAINT we measure local Pol II antibody counts and estimate total nuclear abundance.

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Johannes Stein @jmstein.bsky.social · Aug 13

(5/n) More binding events enable:

•⚡ Efficient kinetic filtering to remove non-specific localizations
•🎯 High-fidelity antigen profiling down to single-antibody

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