Hamed Najafabadi

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ...

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Transcriptional interferences ensure one olfactory receptor per ant neuron
www.nature.com/articles/s41...

Caviar for RNA-Seq nerds! Check this out

📣 Attention #RNA #Splicing lovers! How is splicing of exons coordinated??🤔 ➡️ Exon Junction Complex (EJC) coordinates inclusion of blocks of neighboring exons!😯 Cool work by Alexandra Bergfort @karlaneugebauer.bsky.social lab - check it out! (we got to help a bit 😊) genesdev.cshlp.org/content/earl...

🚨 New paper alert on telomeres! 🚨
Something different from the group! Thanks to Yuxin, a talented student in the lab, we used long-reads in 75 human trios to study telomeres and their inheritance.

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.

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

The DND1-NANOS3 complex shapes the primordial germ cell transcriptome via a heptanucleotide sequence in mRNA 3'UTRs The RNA-binding proteins DND1 and NANOS3 are essential for primordial germ cell survival. Their co-immunoprecipitation and overlapping loss-of-function phenotypes suggest joint function, yet how they ...

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

Delighted to share the story of two germline RBPs - one with little (DND1) and one with no (NANOS3) intrinsic sequence-specificity - that together build a continuous RNA binding surface recognizing a 7-mer (AUGAAUU) in target mRNA 3’UTRs, leading to deadenylation.

Activity of most genes is controlled by multiple enhancers, but is there activation coordinated? We leveraged Nanopore to identify a specific set of elements that are simultaneously accessible on the same DNA molecules and are coordinated in their activation. www.biorxiv.org/content/10.1...

REST/NRSF Preserves muscle stem cell identity by repressing alternate cell fate - Nature Communications Here the authors show that REST/NRSF represses non-muscle lineage genes in muscle stem cells and progenitors, preserving their identity and differentiation capacity. Loss of REST disrupts gene silenci...

Delighted to share our latest paper out @NatureComms. REST/NRSF is essential for muscle stem cell identity, blocking alternate cell fates—huge congrats to the first author @KorinSahinyan and the rest of the fantastic coauthors.
www.nature.com/articles/s41...

A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage A phylogenetic approach reveals cryptic LTR subfamilies and functional insights at nucleotide resolution in primates.

Is the annotation of viruses in the human genome accurate? We think not. Take a look at our new paper and let us know if you agree! www.science.org/doi/10.1126/...

Identification of conserved RNA regulatory switches in living cells using RNA secondary structure ensemble mapping and covariation analysis - Nature Biotechnology Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

I am so incredibly excited to share our latest work, on the exploration of #RNA secondary structure ensembles and discovery of RNA regulatory structural switches in bacteria and human cells, just out in
@natbiotech.nature.com: nature.com/articles/s41.... A short tread! (1/n)

Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression Zinc finger proteins (ZNFs) are the largest family of transcription factors, yet how they activate gene expression remains unclear. In this study, we identified Zincore, a protein complex consisting o...

In today’s publication in Science we introduce Zincore: a novel protein of QRICH1 and SEPHS1 and functions as a transcriptional coregulator dedicated to zinc finger transcription factors. Here’s how we found it: 🧵 www.science.org/doi/10.1126/... 1/11

Hello out there! Are you looking for a friendly community to share your RNA research and hear about some cool RNA biology? Register for @trendrna.bsky.social on July 10-11 now! Oral abstract deadline is May 30th! Co sponsored by @rnacanada.bsky.social!

Perspective on recent developments and challenges in regulatory and systems genomics Abstract. Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regul

Our New perspective explores breakthroughs & challenges in regulatory & systems genomics: from cis-regulatory code & 3D chromatin to spatial omics & AI models.
🔗 doi.org/10.1093/bioa...
#Genomics #Bioinformatics #RegulatoryGenomics

Dissecting regulatory syntax in human development with scalable multiomics and deep learning Transcription factors (TFs) establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility, and regulating gene expre...

Delighted to share our latest work deciphering the landscape of chromatin accessibility and modeling the DNA sequence syntax rules underlying gene regulation during human fetal development! www.biorxiv.org/content/10.1... Read on for more: 🧵 1/16 #GeneReg 🧬🖥️

Delighted to see this out! Fun fact: I actually started my lab @ UCSF w/ goal of understanding tRNA txn regulation, which aligned perfectly w/ @genophoria.bsky.social & Sohail! 6+ years of amazing collaboration & stellar work by Siyu, Albertas, & co & we're making real progress w/ more to come!

Alternative splicing (AS) is common, but its impact on the proteome remains debated, especially in primary cells.

What determines which AS isoforms result in abundant proteins ?

We find that proteoform-specific ...

🧵
www.biorxiv.org/content/10.1...

Really nice work! Congrats!

our work on the molecular differences between transcription factor isoforms is out now in Molecular Cell!

key point: 2/3rds of TF isos differ in properties like DNA binding & transcriptional activity

many are "negative regulators" & misexpressed in cancer

www.sciencedirect.com/science/arti...

Dissecting the RNA binding capacity of the multi-RRM protein Rrm4 essential for endosomal mRNA transport RNA-binding proteins (RBPs) utilize multiple RNA-binding domains (RBDs) to engage with extensive mRNA networks. Understanding the intricate interplay of modular RBDs is essential for uncovering RBP fu...

Why do RBPs need multiple RNA-binding domains? We show transcriptome-wide that the endosomal mRNA transporter Rrm4 uses its three RRMs to differentiate functional binding sites from accessory ones. Great collaboration with @koenig-lab.bsky.social and Zarnack lab
www.biorxiv.org/content/10.1...

Tahoe-100M: A Giga-Scale Single-Cell Perturbation Atlas for Context-Dependent Gene Function and Cellular Modeling Building predictive models of the cell requires systematically mapping how perturbations reshape each cell's state, function, and behavior. Here, we present Tahoe-100M, a giga-scale single-cell atlas ...

@thejohnnyyu.bsky.social, @therealnima.bsky.social, and I, are excited to tell you about Tahoe-100M! The largest publicly available single-cell dataset that measures the effect of 1200 genes on 50 cell line models. The Vevo team has outdone itself. #Tahoe100M www.biorxiv.org/content/10.1...

Simultaneous immunomodulation and epithelial-to-mesenchymal transition drives lung adenocarcinoma progression Lung cancer remains the deadliest cancer in the United States, with lung adenocarcinoma (LUAD) as its most prevalent subtype. While computed tomography (CT)-based screening has improved early detectio...

How do early lung tumors evolve?

Our latest preprint, led by Junbum Kim, maps early-stage cancer at single-cell resolution, revealing two key pathways:
🦠Driven by immune activity
🛠️ Driven by fibrosis
These insights could refine detection & treatment.

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

Thrilled to share LUNA🌕 – our new generative AI model that reassembles tissue structures from dissociated cells! LUNA learns spatial priors over existing spatially resolved datasets with the aim to predict cell locations de novo.

Check out our paper here: www.biorxiv.org/content/10.1...

I love this insight on building teams from @genophoria.bsky.social, Core Investigator at Arc Institute, which just released Evo 2: the largest AI model for biology to date.

Catch the full conversation:
+ YouTube: youtu.be/sWcoslBueiE
+ Spotify: spoti.fi/4hLk3xo
+ Apple Podcasts: apple.co/40sQCu9

Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus In eukaryotes, DNA-associated protein complexes coevolve with genomic sequences to orchestrate chromatin folding. We investigate the relationship between DNA sequence and the spontaneous loading and a...

Our latest work: how can compartmentalization emerge in a eukaryotic genome lacking canonical heterochromatin?
By investigating bacterial genomes put in yeast, we show that the presence or absence of transcription is sufficient!
#chromatin #3Dgenome #generegulation
www.science.org/doi/10.1126/...
👇

A generative framework for enhanced cell-type specificity in rationally designed mRNAs mRNA delivery offers new opportunities for disease treatment by directing cells to produce therapeutic proteins. However, designing highly stable mRNAs with programmable cell type-specificity remains ...

The first preprint of 2025! Together with Matvei, @halfacrocodile.bsky.social, & our amazing team, we are excited to share PARADE: an AI framework for designing mRNA UTRs with enhanced cell-type specificity & stability. www.biorxiv.org/content/10.1...

Very excited to announce that the single cell/nuc. RNA/ATAC/multi-ome resource from ENCODE4 is now officially public. This includes raw data, processed data, annotations and pseudobulk products. Covers many human & mouse tissues. 1/

www.encodeproject.org/single-cell/...

A unified model for interpretable latent embedding of multi-sample, multi-condition single-cell data - Nature Communications Single-cell analysis of multi-condition cohorts requires modelling the interaction between sample variables and cell states. Here, authors develop GEDI to enable integration, cluster-free differential...

Glad to see this work is out! Congratulations! We also included LEMUR in a (non-comprehensive) comparison of DE analysis methods here: www.nature.com/articles/s41...

Check out this systematic benchmark of genome-wide, annotation agnostic DNALMs & strong baseline ab-initio models for biologically meaningful tasks in regulatory genomics 1/

On December 6, we remember:

Geneviève Bergeron
Hélène Colgan
Nathalie Croteau
Barbara Daigneault
Anne-Marie Edward
Maud Haviernick
Maryse Laganière
Maryse Leclair
Anne-Marie Lemay
Sonia Pelletier
Michèle Richard
Annie St-Arneault
Annie Turcotte
Barbara Klucznik-Widajewicz

This is bound to be an amazing resource!