Pedro Rocha

Poising and connectivity of emergent human developmental enhancers in the transition from naive to primed pluripotency In primed human pluripotent stem cells (hPSCs) resembling post-implantation epiblast, numerous lineage-specific enhancers assume the poised chromatin state, co-marked by H3K4me1 and Polycomb-associate...

Many enhancers that drive tissue-specific gene expression are already connected to gene promoters in human pluripotent cells.

In a new preprint, we share some clues about when, how, and why this happens!

www.biorxiv.org/content/10.1...

Loop extrusion provides mechanical robustness to chromatin Chromosomes are complex biopolymers folded into dynamic loops via a loop extrusion process and may experience various mechanical forces in vivo . We develop a force-dependent model of chromatin loop e...

New preprint from the lab !! Loop extrusion may provide mechanical robustness to chromatin. Great work by Hossein Salari. @cnrs.fr @lbmcinlyon.bsky.social
www.biorxiv.org/content/10.1...

Morphogen and juxtacrine signalling dynamically integrate to specify cell fates with single-cell resolution Morphogen gradients guide tissue patterning but do not act in isolation. How they integrate with other signalling modalities, like juxtacrine signalling, and how these integrations influence pattern r...

Interested in morphogens and how they can robustly specifiy different cell types with single-cell resolution?
Check out this preprint combining experiments and modelling by our colleagues and partners in crime @ucl-cdb.bsky.social:
www.biorxiv.org/content/10.1...

🚨Please share! We are hiring a post-doc! 🪱 🐀
Job posting: www.training.nih.gov/jobs/pdf-gb-...
Lab Website: www.niddk.nih.gov/research-fun...
NIH Trainee info: www.training.nih.gov

Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇

The eukaryotic replisome intrinsically generates asymmetric daughter chromatin fibers DNA replication is molecularly asymmetric, due to distinct mechanisms for lagging and leading strand DNA synthesis. Whether chromatin assembly on newly replicated strands is also asymmetric remains un...

Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up!
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)

Computational image analyst (m/f/d) The Max Planck Institute for Molecular Biomedicine in Münster, Germany, has an opening for a

My lab @mpi-muenster.bsky.social is looking for a computational biologist with a passion for imaging and spatial biology. A staff scientist position with long-term perspective! Apply and spread the word 🙏 jobs.mpi-muenster.mpg.de/jobposting/0...

In our latest preprinted work, Yajie and Kostas combine computational analysis with precision KO of single variant U1 snRNA genes in human iPSCs to find pronounced deregulation of both gene expression and splicing that seem to affect the cell cycle and the differentiation potency of stem cells. 1/n

Epigenetic relay: Polycomb-directed DNA methylation in mammalian development In mammals, repression of germline-specific gene expression is essential for preserving somatic cell identity and preventing disease. Germline gene silencing is often dependent on the presence of prom...

Very excited to share an excellent review from @teresa-urli.bsky.social, published one week before her PhD defense! We did a deep dive into the fascinating biology of the variant Polycomb complex, PRC1.6 (1/5) journals.plos.org/plosgenetics...

Figure 1 - Live imaging of endogenously tagged YAP-miRFP670, mScarlet-I-SOX2 and CDX2-eGFP during the first fate decision in preimplantation embryos. (A) A developmental timeline of trophectoderm (TE) and inner cell mass (ICM) specification. The first cell differentiation event, between the TE (green) and ICM (purple), initiates at the 16-cell stage, establishing distinct inner, ICM, and outer, TE, cell populations in the 32-cell stage embryo. Embryos in this study are imaged until the 32-cell stage. Days post-fertilization are denoted by embryonic day. (B) Sox2 and Cdx2 expression is regulated by YAP. In ICM cells, YAP is phosphorylated and retained in the cytoplasm, facilitating Sox2 expression. In TE cells, YAP is predominantly localized to the nucleus where it activates expression of Cdx2. (C) Time-lapse images of a representative embryo expressing YAP-miRFP670, mScarlet-I-SOX2 and H2B-miRFP670 from the 8-cell through the late 32-cell stage. A z-stack was acquired every 15 min for YAP and H2B channels, and every 30 min for the SOX2 channel. Maximum intensity projections (MIPs) are shown. Unit of time is hours. Scale bar: 10 µm. (D) Time-lapse images of a representative embryo expressing YAP-miRFP670, CDX2-eGFP and H2B-miRFP670 from the 8-cell stage through the late 32-cell stage. Scale bar: 10 µm.

Mathematical modelling of the first fate decision

This Research Highlight showcases the work from Maria Avdeeva, Madeleine Chalifoux, Bradley Joyce, Stanislav Y. Shvartsman, Eszter Posfai @eposfai.bsky.social :

journals.biologists.com/dev/article/...

Job add showing the lab logo and the following text: WHAT WE OFFER Fully-funded fellowships up to five years Opportunity to start your own research program or lead ongoing projects. Large, diverse and extraordinary scientific network at the NIH/Bethesda campus. Working at NIH offers the possibility of living in a diverse, liberal and vibrant city: Washington DC Or in a calm residential area with great schools and good affordable housing: Bethesda and Rockville. WHO YOU ARE You share our enthusiasm for epigenetics, gene regulation, nuclear organization and mouse development. You have PhD-experience in one or more of the following: mouse development, mouse genetics, epigenetics, or computational biology.

🚨🚨🚨 Please repost
We are looking for postdocs to join our lab at NIH.
Apply:
www.nichd.nih.gov/research/atNICHD/Investigators/rocha/apply
Learn more about training at NIH :
www.training.nih.gov/research-tra...

📢 New in @ImmunityCP: We have mapped the transcription factor “routes” that program two dendritic cell subsets opening paths for personalized #cancer #immunotherapy. Read it here: doi.org/10.1016/j.im...
Here is a summary of what we discovered 🧵:
Illustration by @azuravesta.bsky.social

Liver-specific loss of Atg9a perturbs lipid metabolism and hepatocyte integrity The autophagy-related protein ATG9A is integral to cellular autophagy and lipid mobilization, yet its importance in mammalian physiology remains underexplored. Using a liver-specific conditional At...

Excited to share the first paper from the lab! 🥳 The ATG9 and lipid droplets saga continues! Open source!

I'm really happy to announce that my two main postdoctoral works have been published in the same issue of Developmental Cell! First, the final form of the mouse cortical organoid protocol (tinyurl.com/bddfmx8n), which I recently presented at Development presents (tinyurl.com/36udcpme) and…

Enhancer remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm Correct patterning of emerging tissues in the developing embryo is essential for the formation of functional organ systems. Using genetic tools for controlled protein depletion, Ee et al. identify the...

Excited to share our new study in @cp-devcell.bsky.social dissecting how the brain-associated transcription factor OTX2 drives anteriorization of the mammalian gut by enhancer remodeling using stem cell-based models. #development #enhancers #patterning #stemcells

www.cell.com/developmenta...

We chose to forget that.

NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

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 ...

🚨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...

Our faculty job market series continues today on the topic of CVs, cover letters, and LORs. Come hear myself, @brisapalikuqilab.bsky.social & @jayeperview.bsky.social share our thoughts/advice today at 3pm ET / 12p PT. There will also be time for Q&A.

Registration link in flyer - see you soon!

MLL2 facilitates long-range gene regulation through LINE1 elements Transcriptional regulation is tightly linked to chromatin organization, with H3K4me3 commonly marking both active and bivalent promoters. In embryonic stem cells (ESC), MLL2 is essential for H3K4me3 d...

#Preprint alert! 📣

We are thrilled to share the work led by Lara Zorro-Shahidian and Lucio di Filippo, in which we show that #MLL2 controls gene expression in both #ESC and upon #differentiation by facilitating the #enhancer like activity of #LINE1 elements

www.biorxiv.org/cgi/content/...

Joint decomposition of Hi-C maps reveals salient features of genome architecture across tissues and development The spatial organization of chromosomes in the nucleus is fundamental to cellular processes. Contact frequency maps from Hi-C and related chromosome conformation capture assays are increasingly availa...

We're excited to share our new preprint, "Joint decomposition of Hi-C maps reveals salient features of genome architecture across tissues and development", led by Thomas Reimonn. www.biorxiv.org/content/10.1...

Very cool. Looking forward to reading it in detail.

Synthetic engineering demonstrates that synergy among enhancers involves an increase in transcriptionally productive enhancer-gene contacts Enhancers are non-coding cis-regulatory elements that control the expression of distally located genes in a tissue- and time-specific manner. Recent studies indicate that enhancers can differ in their...

Excited to share the latest work from the lab led by @eharo84.bsky.social, in which we have used synthetic biology to explore the mechanisms by which different types of long-range enhancers ensure robust and precise developmental gene expression

www.biorxiv.org/content/10.1...

Programmed meiotic errors facilitate dichotomous sperm production in the silkworm, Bombyx mori The goal of meiosis is typically to produce haploid gametes (eggs or sperm). Failure to do so is catastrophic for fertility and offspring health. However, Lepidopteran (moths and butterflies) males pr...

So excited to share this preprint from the Rosin lab in collaboration with the Hawley lab and @eelcotromer.bsky.social on moth spermatogenesis! We investigate the meiotic errors that occur during the formation of apyrene sperm (that have no DNA) in silkworms!

www.biorxiv.org/content/10.1...

Thrilled to share our work using live imaging to understand how Epiblast (future embryo proper) and Primitive Endoderm (future extraembryonic tissues) cell fates segregate in the preimplantation mouse embryo. Gargantuan effort led by amazing @rpkimyip.bsky.social, David Denberg and Denis Faerberg!

SUMO operates from a unique long tandem repeat to keep innate immunity in check Abstract. The SUMO pathway mainly functions to repress innate immunity in myeloid cells. Inactivating sumoylation triggers a strong, noncanonical, type I i

🚨🚨🚨 New collaborative results with Anne Dejean (@institutpasteur.bsky.social ) and very talented PhD student Amandine Goffeney. academic.oup.com/nar/article/... Trying to understand how SUMO represses innate immunity and IFNB1, we discovered an element with a unique function in 3D 🧬🧬🧬 organization

Group Leader - Genome Biology Unit Are you ready to lead groundbreaking research in Genome Biology? Join us at EMBL! We are seeking a motivated scientist to lead an independent research group addressing exciting and original biological...

To all post-docs: The Genome Biology dept ‪@embl.org
has an Independent faculty position. Fantastic place to set up your lab –great package: core funding, fantastic Ph.D. students, cutting edge core facilities & great colleagues. Closing date Sept 19th
embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

Thanks to @riyavsinha.bsky.social in my lab, the IGV browser will natively support dynseq (dynamic sequence tracks) in an upcoming release. These tracks are very useful to directly visualize base-resolution scores (e.g. contribution scores from ML models, conservation etc). 1/

How do enhancer-gene contacts relate to transcription activation? In mouse embryonic stem cells, a combo of STED, oligoFISH & RNA FISH shows that 3% of Dppa3 alleles transcribe. For these, enhancers and promoters come closer (panel E). Stumberger ... Leonhardt & Harz www.biorxiv.org/content/10.1...

Somatic cells compartmentalise their metabolism to sustain germ cell survival To ensure success in reproduction, organisms dedicate substantial resources to supporting the germline. In testes, somatic gonadal cells form a barrier that isolates germ cells from circulating nutrie...

🆕🧪‼️
New lab preprint!
We study how germ cells (the cells that give rise to gametes, in this case sperm) are supported by somatic (non-germ) cells of the gonad. This matters for our understanding of reproduction - without germ cell development, animals are sterile.
www.biorxiv.org/content/10.1...