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Josh Brickman @josh-brickman.bsky.social · Aug 12

Looking forward to Naama Barkai's visit tomorrow - all in copenhagen interested in biological specificity should come to hear her talk tomorrow!!!!

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Josh Brickman @josh-brickman.bsky.social · Aug 11

Contributions from our side, Martin Proks @nazsalehin.bsky.social and Madeleine Linneberg-Agerholm, whose original in vitro finding are validated in this paper - journals.biologists.com/dev/article/...

Naïve human pluripotent stem cells respond to Wnt, Nodal and LIF signalling to produce expandable naïve extra-embryonic endoderm | Development | The Company of Biologists

journals.biologists.com

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Josh Brickman @josh-brickman.bsky.social · Aug 11

Our model suggests that a few cells can partially differentiate, forming early endoderm that still expresses some epiblast markers - this could be due to the differences in timing of the two binary cell fate choices in preimplantation development between mouse and human.

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Josh Brickman @josh-brickman.bsky.social · Aug 11

We used our deep learning models that were originally published in www.nature.com/articles/s41...

Deep learning-based models for preimplantation mouse and human embryos based on single-cell RNA sequencing - Nature Methods

This Resource uses deep learning-based tools to build a dynamic transcriptomic reference for mouse and human preimplantation development.

www.nature.com

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Josh Brickman @josh-brickman.bsky.social · Aug 11

Very happy to see this nice collaboration with @niakanlab.bsky.social bear fruit. Beautiful work by @clairesimon.bsky.social culturing human embryos in the presence of FGF/ERK stimulation/inhibition. www.nature.com/articles/s41...

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst - Nature Communications

The authors show human embryo lineage specification in the blastocyst is driven by differential FGF/ERK signaling, which segregates yolk sac-fated hypoblast and embryonic epiblast. They establish naïv...

www.nature.com

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Josh Brickman @josh-brickman.bsky.social · Jun 24

Back from the ISDB,
Clearly my presence in the lab was missed!

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Josh Brickman @josh-brickman.bsky.social · Jun 2

Why combat aging with enhancers at 11? Why not just make 10 louder? It wouldn't be 11. For transcription, all the other processes (translation, splicing etc) are on ten, on ten, etc…where do they go? For Enhancers, everything on ten, the transcription factors deacetylate and go one higher, 11.

The EMBO Journal @embojournal.org · Jun 2

Issue 11
N&V: fibroblast dynamics during mammary oncogenesis
RIPK1 oligomers at core of CD95 necrosomes
Autophagosomes as hub for AKAP regulation of neuronal PKA
Centipede neurotoxin reveals new mode of Nav channel modulation
Cover: @josh-brickman.bsky.social et al
www.embopress.org/toc/14602075...

This cover highlights the article Altering metabolism programs cell identity via NAD+-dependent deacetylation by Robert A. Bone, Joshua M. Brickman and colleagues. The front cover illustration depicts an audience of embryonic stem cells consuming galactose, silencing background epigenetic noise, so that they can better “hear” the signal from the “Transcription Factors”. The band (key transcription factors) are deacetylated (their leather jackets are removed) by sirtuins (the roadies) to amplify the lineage-specific enhancer signal, at the same time as deacetylation of histones to reduce the availability of non-specific enhancer sequences. The state of both lineage-specific and non-specific “Enhancers” is indicated by their output (via the amplifier). The net result is that cellular instructions are better discernable, and the audience becomes energized.

Cover concept by the authors, scientific illustration by SciStories

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Josh Brickman @josh-brickman.bsky.social · May 28

Thanks for that !

Josh Brickman @josh-brickman.bsky.social · May 25

Another chapter from Martin Proks PhD. The first chapter in our nf-core saga and a new pipeline for MARS-seq! academic.oup.com/bioinformati...

nf-core/marsseq: systematic preprocessing pipeline for MARS-seq experiments

AbstractMotivation. Single sequencing technology (scRNA-seq) enables the study of gene regulation at a single cell level. Although many sc-RNA-seq protocol

academic.oup.com

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Josh Brickman @josh-brickman.bsky.social · May 25

Very nice paper - all principles at the heart of molecular biology although the logic with which evolution implements them was a mystery.

Lars Velten @larsplus.bsky.social · May 8

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵

Design principles of cell-state-specific enhancers in hematopoiesis

Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

www.cell.com

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Josh Brickman @josh-brickman.bsky.social · May 22

Alba Redo Riveiro - an amazing PhD student. One chapter in her PhD is described here. It was a great paper and a very long evolving story - www.cell.com/stem-cell-re...

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Josh Brickman @josh-brickman.bsky.social · May 20

Very excited to see Melissa elected to the Royal Society. Nice triumph for old school developmental biology entering the modern world of translation. Way to go Melissa!!!!
renew.ku.dk/latest-news/...

reNEW CEO named Fellow of the Royal Society

renew.ku.dk

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Josh Brickman @josh-brickman.bsky.social · May 9

And wait to you see the accompanying image that goes to 11!

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Josh Brickman @josh-brickman.bsky.social · May 9

And here I was thinking I need to modernize my references with Taylor - perhaps the Last Dance is further away then we think!

Sally Lowell @cellysally.bsky.social · May 8

Congrats Josh! Was just thinking of you while listening to this new Mekons session. Your ##PaperThemeTune can be the first track: it lacks chromatin, but does contain an age-appropriate dose of nostalgia... www.bbc.co.uk/sounds/play/...

Riley & Coe - Mekons live in session! - BBC Sounds

Marc is joined by legendary punk rockers Mekons live from the BBC's Maida Vale studios.

www.bbc.co.uk

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Josh Brickman @josh-brickman.bsky.social · May 7

Two days left to apply to do fantastic science in a great place - come join us as a new group leader at reNEW - employment.ku.dk/faculty/?sho...

Junior Group Leader (Associate Professor) in Stem Cell Medicine

employment.ku.dk

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Josh Brickman @josh-brickman.bsky.social · Apr 25

This enhanced or deteriorating ratio of epigenetic signals may also underpin aging. Amazing work by Robert Bone @alboo87
, @molly_lowndes
and Collaborators @treebak
and Michael Nielsen, all of @LabBrickman
in @reNEW_Global
@UCPH_health

Josh Brickman @josh-brickman.bsky.social · Apr 25

Imagine you take your grandparents to a crowded restaurant, they complain they can’t hear you both because you aren’t speaking loud enough, and that there is too much noise.

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Josh Brickman @josh-brickman.bsky.social · Apr 25

SIRT1 in turn, turns up the signal to noise ratios at the level of enhancer regulation, with 14K enhancers become 4K very effective enhancers.

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Josh Brickman @josh-brickman.bsky.social · Apr 25

Super ESCs, rejuvenated ESCs, enhanced lipid metabolism leads to elevated NAD and activated SIRT1

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Josh Brickman @josh-brickman.bsky.social · Apr 25

Essentially, we tried giving cells their own variation on Ozempic…Galactose. In the case of ESCs, we bypass the brain and substitute galactose for glucose the media…they become super stem cells.

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Josh Brickman @josh-brickman.bsky.social · Apr 25

How does metabolism act through generic chromatin modifiers promote specific cellular states? Simultaneous modification of transcription factors and chromatin, enhancing epigenetic signal to noise ratios.
www.embopress.org/doi/full/10....

Altering metabolism programs cell identity via NAD+-dependent deacetylation | The EMBO Journal

imageimageHow alterations in cell metabolism translate into specific developmental gene programs remains a major question. This study shows that forcing OXPHOS metabolism reprograms mouse embryonic stem cells (ESCs) to a more inner cell mass (ICM)-...

www.embopress.org

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Reposted by Josh Brickman

The EMBO Journal @embojournal.org · Apr 25

Altering metabolism programs cell identity via NAD+-dependent deacetylation
@josh-brickman.bsky.social et al show enforced OXPHOS dependence in embryonic stem cells drives deacetylation of essential transcription factors & inner-cell-mass-like gene expression
www.embopress.org/doi/full/10....

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Josh Brickman @josh-brickman.bsky.social · Mar 3

Really looking forward to a day in Sheffield - one of the first places
In the world to work with human pluripotent cells!

Development, Regeneration and Neurophysiology @drn-sheffield.bsky.social · Mar 3

Today we welcome Josh Brickman @josh-brickman.bsky.social from reNEW at the University of Copenhagen, who will present his work on transcription factors and cellular memory.

Alfred Denny Conference Room, 1 pm. All welcome!

Host: Anestis Tsakiridis @tsakiridis.bsky.social

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Reposted by Josh Brickman

Carmelo Ferrai @carmeloferrai.bsky.social · Feb 2

PRC2 promotes canalisation during endodermal differentiation

journals.plos.org/plosgenetics...

@Robertillingwo7 @wbickmor.bsky.social
@josh-brickman.bsky.social

PRC2 promotes canalisation during endodermal differentiation

Author summary Embryogenesis requires a tightly coordinated programme of cellular expansion and specialisation to gives rise to all of the cell- and tissue-types of the developing organism. In mammals...

journals.plos.org

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Josh Brickman @josh-brickman.bsky.social · Feb 2

What does PRC2 do? It keeps the differentiation train on the rails, insuring lineage fidelity!

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