Josh Brickman
@josh_brickman
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Developmental and Stem Cell Biologist, Interested in the transcription, lineage specification, potency and plasticity. Mastodon -
Copenhagen
Joined January 2014
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Latest in our Plasticity Project, featuring our fave cells, Primitive Endoderm (PrE), and their in vitro model, nEnd. Amazing PhD journey
@MLAgerhom
, contributors
@AnnikaCharlott2
@albooo87
@MartaPrera
@mproksik
@TeresaKnudsen
@MigManzanares
(1/11).
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Very grateful to
@ERC_Research
for the
#ERCAdG
- SENCE: Signaling decoded in ENhanCEr states – a molecular basis for plasticity in development and differentiation. A fantastic opportunity to delve into transcription factor(TF) persistence and plasticity in regulative development.
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Excited for the end of a long and winding road just published published -. Evolution of OCT4 and naïve/primed pluripotency. Protein evolution occuring via tweaks domain orientation rather than mutations in the domains themselves.
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Very happy to share our signalling enhancer opus. Very proud of
@LabBrickman
. Tremendous effort by first author, the talented
@WilliamBHamilt1
, support from
@ritasmonteiro
,
@TeresaKnudsen
, and our collaborators
@jespervolsen
,
@kbemdal
,
@BarkaiNaama
.
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Very pleased to share our latest opus on
#transcription
factor cooperativity and differentiation competence.
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Very happy to be elected to EMBO - want to thank all past and present members of
@LabBrickman
for their amazing contributions over the years!
Outstanding scientists elected to EMBO Membership: in EMBO’s 60th anniversary year, 100 new members and 20 associate members join the community
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Interested in how transcription factors encode cellular memory and predict future cell states. How they regulate plasticity or potentiality, rather than identity. Think about coming to
@LabBrickman
for either a PhD
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Ever wondered what aspect of human development (months) is missing from in vitro PSC differentiation (weeks) – growth; not just for cell number, but to prep enhancers for further differentiation!
Beautiful -
@YanFungWong
, Yatendra Kumar
@wendy_bickmore
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Are enhancers promoters? Nice discussion on the spectrum of "promoter-ness," and "enhancer-ness," and the notion that unstable bidirectional transcription maybe a useful for enhancer identification.
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As a student we were taught, “no experiments could show chromatin did more than salt,” but now with the amazing
@groth_anja
+
@robin_andersson
;
@AliceScientist
,
@BiranAlva
,
@NicoAlc82
&
@albooo87
show pluripotency required balanced epigenetic inheritance!
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Another paradigm destroyed by
@BarkaiLab
- . Previously they found DNA binding domains were not important and now
#cooperativity
is minimal and unidirectional. How to explain specificity? I am lost!!!!
#papertunes
- Iggy/the Stooges, “Search and Destroy.”
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Transcription is a better insulator than insulators themselves? Hmmmmm, interesting….
CTCF, BEAF-32, and CP190 are not required for the establishment of TADs in early Drosophila embryos but have locus-specific roles
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Want to explore transcription and developmental plasticity or how signalling regulates enhancer activity via preformed TF-enhancer complexes? PhD students and post-doc positions available on our ERC Adv grant SENCE. Please RT
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Finally, after two postponements, the stem cell nice is back…thanks to the
@novonordiskfond
- all costs on the ground (i.e. except travel to Denmark) covered. An amazing meeting!!! Applications open in January!
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How do cells compute choices and support indecision? How is indecision exploited in self-renewal?
@TeresaKnudsen
adressed these questions, focusing on endoderm and epiblast specification. Interested? Check out our new new paper from
@reNEW_Global
.
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Deadline extended!!!!! Apply for an intense and exciting meeting experience, a Gordon conference on steroids…the
@novonordiskfond
covers all local expenses - you just have to get to Denmark…new deadline - 20th of February!
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After having crawled back from being under a rock better known as grant deadlines I woke up to Twitter and just in time to share our latest opus on multi-lineage (embryonic and extra-embryonic) differentiation or “Experimental totipotetncy.”
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So this trumps SELEX!!!! '
Transcription factor binding site orientation and order are major drivers of gene regulatory activity - Nature Communications
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Shadow enhancers coming out of the shadows! It was always hard to imagine that they were just about robustness -
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Great to see a symposium named for Rosa Beddington, a pioneer of modern mammalian developmental biology with a innate appreciation of the embryo's aesthetic and valued mentor - 1st Crick-Beddington Developmental Biology Symposium via
@the_Node
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Enhancers get further from promoters when transcription is on...kind of difficult to reconcile with the loops depicted in so many text books - fantastic paradigm shifting work from
@wendy_bickmore
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After an almost a year wait - the inauguration of Melissa Little as Professor of Stem Cell and Translational Medicine - a great
@UCPH_health
and
@reNEW_Global
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New collaborations begin
@reNEW_Global
#ASM
- my new colleague tells me about the origins of trophoblast…but unlike us Eutherians he/she has POU5F1 and 3!
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Almost at the end of a fantastic meeting on
#epigenetics
and
#development
- one of the most exciting conferences on this subject in sometime -
@MaharshiDeb
and
@srimontagayen
did a fantastic job
@iiscbangalore
- and nice to have special guests for lunch!
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Finally Dr Morgantini - way to go
@labBrick
man, already 2 PhDs already this year
@renew_global
🎉
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Interesting in plasticity? Enhancer regulation by signaling? How we access the information in our genomes? Come to lovely Copenhagen and join one of our projects focused on the above questions in early development and stem cell biology. - please RT
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Congratulations to Dr. Perera -
@MartaPrera
- a lovely defense with great discussion. Thanks to
@amyralston
and Liz Robertson. I and all
@LabBrickman
will miss this incredibly talented embryologist!
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Pleased to present the enduring work of
@albooo87
with help a former
@LabBrickman
member
@JasAlMousawi
who ran to of to Rome, and beautiful additions from
@MLAgerholm_
@mproksik
and
@MartaPrera
- a veritable feast of cooperative interactions!
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A new model for preimplantation development, both mouse and human, taking advantage of neural networks to both build/integrate and classify cell types. Beautiful work by
@mproksik
and
@nazsalehin
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Ever wonder what controls sequence specific activation of signaling – much to our surprise its not activation, thanks
@MartaPrera
and her new model for ERK induction in vivo
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Just coming from MCMB
@The_MRC
- this board has historically been about funding the best in fundamental biology/medical research and it still is! Please send in your grants and don't worry if they are not translational, just excellent science!
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Celebrating publication of - first time three first authors have been together in person since before the pandemic!
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While the cell cycle is clearly linked to self renewal/differentiation, its role in gene regulation/differentiation/renewal can be conveniently ignored; here is a nice review covering the cell cycle in pluripotency, reprogramming and neural stem cells -
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Are you interested in transcriptional regulation?
@Brickman_lab
in
@reNEW_Global
is looking for a PhD student/post doc to exploit enhancer regulation to develop better human stem cell embryo models and approaches to differentiation!
Please RT
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OCT4 and SOX2 sitting at genes that dynamically respond in ESCs, both those that are on and off.
Interesting and supports the idea that some TFs establish a foundation that can be built on in different ways, as signalling changes instruct transcription.
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The deadline for the "Stem Cell Niche" is the 12th of February. A fantastic experience, like a Gordon Conference, in an amazing environment! Lots of opportunity for short talks and discussion! All local costs covered for accepted applicants! Apply at
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Very happy to be a part of this new initiative spear headed by Melissa Little - our new CEO and Executive Director. Exciting opportunities for stem cell research that open new vistas in a translational direction with
@MCRI_for_kids
and LUMC and a new NNF center
@UCPH_health
!
A grant from the Novo Nordisk Foundation of up to 300 million euro now enables the establishment of a major international research center focused on stem cell medicine.
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A great demonstration that fundamental developmental biology is relevant to IVF failure...non aneuploid phenotypes that highlight links between metabolism, epigenetics and developmental progression!
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Amazing to interact in person, great science and a little fun
@CSHANews
with
@AMartinezArias
@LabTajbakhsh
@anne_grapin
from
#Embryos
to
#StemCell
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A bitter seat moment for
@LabBrickman
and
@reNEW_Global
-
@TeresaKnudsen
spreads her wing. An absolute tremendous PhD and great defense!
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At the weekend I was tested for covid19 and it came back positive. I am fortunate so far, to have a mild case of the disease, but if I had travelled to the meeting, who knows what severe illness I might have caused in others.
I wish everyone well over the next few weeks!
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Congratulations Dr Karolína Ditrych Hvid on a fantastic job defending your PHD - you made all of
@LabBrickman
proud!
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Very interesting discussion of RNA dominance in epigenetic inheritance by
@OdedRechavi
including the potential for permanent alterations to the genome and new interpretations of Luria-Delbrück data
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#Cellfie
- stem cell heterogeneity induced by different culture conditions...brought to you in technicolor.
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Final version of our human hypoblast expansion paper is now out:
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Last night I received a very constructive editorial decision. This has happened more often lately - the influence of
@elife
,
@Dev_journal
,
@PLOSBiology
etc, new generation of editors? Whatever the case, Is not more movement in this direction better than eliminating accept/reject?
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As the words "phase separation," are increasingly bantered about as "conformational change," of contemporay cell biology...here is a critical assessment of experimental evidence
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@reNEW_Global
wins poster and talk prizes…
#CSHAsia
-
@csham
- meeting on Human Development - from
#Embryos
to
#StemCell
-
#Awaji
; a show of force with
@YanFungWong
@JZylicz
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Thoughtful demonstration of GRN dominance over histone modifications in differentiation - loss H3K27me3 has little impact on lineage specific transcriptional regulation, but is required for the stable maintenance of a differentiated state.
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After three days of fantastic discussions with
@LabBrickman
and
@JZylicz
at
#bricklicz
retreat we conclude in Lisbon - some really dynamic thinking with a little fun too!
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Also quite excited by the work of
@MartaPrera
- the first part of her PhD was just published in
@eLife
- amazing finding that selection/differentiation favours increased G1 while shortening the cell cycle.
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Matthew Freeeman’s fall from grace! The decent into cell biology! However whee are the borders between the descending circles of reductionism?
#bsdb18
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@mbeisen
@NIH
Often we don't think about the collateral damage to whistle blowers and other innocent parties in scientific misconduct cases, but institutions often sacrifice them in their paranoid desire to protect themselves. This is a sad reminder that we need to look out for our colleagues.
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Great to be at my first in person conference in a long time and proud of my student
@ChristinaSchuh1
who is at her first meeting, selected for a short talk, managed to tell a separate story from her poster and do a great job!
#FGF_GRC
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Our latest just appeared in
@Dev_journal
- where we demonstrate the generation and expansion of an in vitro human endoderm cell type (nEnd) resembling the early stages of human hypoblast. Fantastic work by first authors
@MadeleineLA93
and Yan Fong Wong.
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How broad is the bottom of the hour glass - very nice discussion of different routes to the phylotypic stage, revisiting the role yolk, the original Yo in the embryo
@YoEmbryo
The evolution of gastrulation morphologies
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Finally we start to understand the difference between TATA containing and TATAless promoters - its all about amplitude not frequency!
Analysis of endogenous fushi-tarazu revealed that misregulation of bursting activities results in disrupted spatial patterning of gene expression.
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After 5 years of planning us!
#stemcellniche2023
was the best yet thanks
@ScienceCluster
@novonordiskfond
and organizers Kim Theilgaard-Mönch,
@kim_bak_jensen
, Ditte Andersen - if someone suggest in 2018 that I would dance to Van Halen/Binjovi and i would have said F…off!
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Happy Birthday Central Dogma - published 60 years ago this month! Nice synopsis of Crick's seminal lecture -
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A very nice piece on pluripotent stem cell therapies and trials highlighting the importance of understanding fundamental mechanisms of development and homeostasis -
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Registration is open for our conference "The Stem Cell Niche," in the broadest sense; extrinsic/intrinsic factors influencing stem/progenitors cells in development and disease- . All local costs paid for accepted participants! Registration deadline 15/2!
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Nice review demystifying a process that was formerly an obscure genetic phenomena and is now central to both
#developmental
biology and
#Cancer
- Cell Competition -
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Big shout out to everyone who helped with , the author authors
@mproksik
@MLAgerholm_
,
@MartaPrera
, Luna Malzard and the rest of
@LabBrickman
in
@reNEW_Global
,
@UCPH_health
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Ever wonder about why ESCs are so plastic, why they enter early differentiation and return in a cycle of dynamic self-renewal. Its all about stoichiometry!
Lovely work by
@TeresaKnudsen
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Interesting in transcription factors and how they regulate plasticity in development and differentiation - only two days left to apply. Please RT
I am retweeting as the links I used no longer work: Want to explore the role of enhancer regulation in early development and differentiation with use, use the following links-
Here is an updated poster
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Had a great time thinking about cellular memory as portrayed by
@SantosLaB8
with
@TeresaKnudsen
; see our preview of their paper @ . The writing process rekindled some multi-cellular memories I had tried hard to destroy
#JohnnyThunders
#Heartbreakers
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Wondering how to generate in vitro stem models for the human hypoblast or mouse primitive endoderm…the lineage never fully recapitulated in
#Blastoids
- see this insightful discussion by
@MartaPrera
of naive extra embryonic endoderm
#nEnd
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An amazing story from a very talented PhD student - soon to submit from her thesis
@LabBrickman
Madeleine Linneberg-Agerholm talking about Regulative development in the preimplantation embryo
@josh_brickman
lab
@reNEW_Global
#NDEVMSS2024
@swedbo
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Nice to see a careful comparison of the impact of genetic background on pluripotency
In the extreme case, one wonders how much culture conditions will need to adapted for different genotypes?
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Once again the
@cphbiosciphd
program is open for application. A fantastic opportunity to do a PhD in an interactive/interdisciplinary/international environment - Interested in
@NNFCPR
@UCPH_DanStem
@Metabolcenter
@DTUBiosustain
. Apply now!
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Another defence begins for
@LabBrickman
- Elena Morganti winds up to defend her PhD
@renew_global
!
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Nice to see that our human hypoblast - nEnd is being used as a standard for primitive endoderm in todays human blastoid papers and - appreciate the new analysis of our data alongside the human embryo - very nice!
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Time is running out and registration deadline approaching for the "stem cell niche," all local cost paid for accepted participants. Fantastic chance to experience a wide range of
#stemcells
,
#development
in a Scandinavian context!
Registration is open for our conference "The Stem Cell Niche," in the broadest sense; extrinsic/intrinsic factors influencing stem/progenitors cells in development and disease- . All local costs paid for accepted participants! Registration deadline 15/2!
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First day back in the lab for an "in person" meeting -
@LabBrickman
left evidence of their excitement to be back....great to see and fantastic to be back!!!
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To disentangle to role of pre-existing TFs from signaling, and exploit signaling to understand the activity of TFs at enhancers. Long live FGF/ERK! Thanks
@ERC_Research
for funding just because we still don’t understand how cells process and use the information in their genomes.
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Exciting evidence that growth is about more than just producing more cells. We find that expansion in a ventral foregut 3D culture prepares enhancers for later organ specific differentiation!
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Was nice to get three scientific generations together on a visit to
@sloan_kettering
-
@Morgani_S
and her grand father Mark Ptashne!
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If you are interested in
#developement
#stemcells
and want to come to the cool city of
#copenhagen
- apply to DanStem. Its a fun place to do fundamental science and a very simple application process!
Join DanStem! We are seeking outstanding scientists for independent research group leader positions at the senior and junior levels. Deadline for application: August 1, 2019. Easy apply by sending a letter of interest to: GL-2019
@sund
.ku.dk.
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More evidence pointing to pluripotency factors being more than guardians of potency, but guides for differentiation - with OCT4 switching from an repressor to an activator at gastrulation! Really nice story from
@MigManzanares
#papertunes
Siouxsie and the banshees "Switch"
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Was really a pleasure to revisit question of plasticity, chromatin, cell cycle and lineage capacity -
@CRGenomica
is an amazing place, didn’t even notice the jet lag!!!
It was a great honour to have
@josh_brickman
to visit the
@DiCroceLab
the all
@CRGenomica
/
@icreacommunity
and discuss novel mechanisms of cell plasticity and differentiation! Big big thanks to
@serg_aranda
for organizing this!!!
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ESCs are defined as "genetically normal, immortal cell lines ..." While there has always been a fear of culture adaptation, this systematic cautionary tail i from Nissim Benvemosty's lab links long term adaptation to cancer related mutations -
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Very happy to contribute with
@power_cardigan
to a collaboration with
@NNFCPR
and Chuna Choudhary's group. Inhibition of p300 impairs RNAPII and basal component recruitment, independently of BRD4 mediated pause release - TFs remain stably associated!
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Stat3 induction reprograms through an early ICM state - nice demonstration that LIF/Stat3 signalling could be more about ICM identity than just epiblast.
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Late night discussions about the cause and effect in epigenetics at the bicklicz retreat
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Nisse strikes again - this time not so nice 😀😀 - but with three variations of this poster all over our floor it was quite an interesting way to wake and before the second cup of coffee too!
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So duration, but not dose….and a slow exit from pluripotency promotes mesoderm differentiation - consistent with the dual function of pluripotency TFs and their stochiometry changing over time in response to combinatorial signaling for alternative fates.
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Very pleased to see my amazing colleague
@groth_anja
receive a
#ERCAdG
- very well deserved! A great achievement for a great lab!
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Reprogramming occurring via primitive endoderm (XEN like), then 2C on the way to pluripotency! This is with small molecules, not TF expression and perhaps under these conditions, reprogramming follows a crude developmental trajectory - ...
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Who would have thought - promoters are intrinsically bidirectional, only gaining directionality through mutation
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A fantastic study led by
@NaikanLab
and
@ClaireSamSimon
- it has been a pleasure to get involved in this collaboration! Fantastic contribution from our side from
@MLAgerholm_
Second cell fate decision: pluripotent epiblast & yolk sac fated hypoblast segregation occurs in an ERK signal-dependent manner in humans, similar to mice, rats & cows.
Team effort led by
@ClaireSamSimon
&
@BournHallClinic
@josh_brickman
@NewcastleFert
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The 2019 Bricklicz retreat finally begins thanks
@ritasmonteiro
and
@MariaPClerigo
- nice to finally be in Cascais!
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An interesting new essay on the concept of self, the microbiome and symbiosis: . Is microbiota an intrinsic component of human nature? Not sure, but a thought provoking discussion.
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Silas celebrating the acceptance of his PloS Bio paper - 4 Simple Rules are Sufficient for Early Mamm Dev - out soon!
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Its that time again - the 2020 Stem Cell Niche meeting went live today at
Remember its a fantastic atmosphere, great meeting, and free to attend for all accepted applicants!!!
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Very nice work from
@briscoejames
and
@t_rayon
- I really like the idea that differences in protein stability (particularly for transcription factors and signalling molecules) could determine rates of differentiation and development -
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