Allon Klein Lab

@LGMartelotto Thank you @LGMartelotto! We still miss you at HMS. Don’t miss the back-to-back paper from Linas Mazutis reporting on another realization of the CAGEs/capsules.

I remember seeing the very first tests in this magical work… Amazing science from ⁦@KleinLabHMS⁩ Multistep genomics on single cells and live cultures in subnanoliter capsules | Science science.org/doi/10.1126/sc…

I just finished reading this beauty from the @KleinLabHMS 🫶🫶🫶 Multistep genomics on single cells and live cultures in subnanoliter capsules. Mazelis et al, recently published Science last December. DOI: 10.1126/science.ady7209 I first saw Ignas start working on this almost five years ago when I was at HMS. It’s unreal, and makes me very happy, to see it go all the way to a Science paper. Legend! In this work, Ignas and team introduce a new single-cell functional genomics platform that lets you: -keep single cells alive -culture them over time -run multi-step biochemical workflows on them -then read out genome-wide signals The big breakthrough is the capsule design. It physically holds cells (and large biomolecules) in place, while still allowing media, enzymes, and reagents to diffuse in and out. Smart idea. Huge impact. To make this work, they built “capsules with amphiphilic gel envelopes,” or CAGEs. These magic capsules: -retain cells and large analytes (so you don’t lose the important stuff) -stay permeable to media, enzymes, and reagents (so complex protocols still work) -support high-throughput processing (so you can scale to tens of thousands of samples) This matters because most functional genomic assays require multiple sequential steps. Those workflows fall apart when you try to scale them across large numbers of living single cells. CAGEs solve that, which allowed the team to: -run high-throughput, multi-step workflows on living single cells (not limited to “one-pot” reactions) -create a DNA library barcoding strategy for CAGE-derived material, so you can pool capsules without losing cell identity -measure how gene expression programs persist through clonal expansion -link lineage-like clonal growth with transcriptome readouts at real scale Most single-cell sequencing methods are great at snapshots. But biology is dynamic. We care about things like: -response to stimuli -stability of cell states -differentiation -expansion of rare clones This platform tackles one of the biggest bottlenecks in the field: Scaling live-cell, multi-step functional measurements to high throughput, while still getting genome-wide readouts!!! Big congratulations to the entire team!

Excited to see this out in Science! We introduce CAGEs (Compartments with Amphiphilic Gel Envelopes): resilient, semi-permeable shells that overcome limits of droplet microfluidics. CAGEs enable “multi-step genomics” at a massive scale. Back-to-back with the Mazutis lab🔥

I am delighted to share that my main PhD project is finally out in Science Magazine! I'm honored to have worked with so many talented colleagues and mentors that guided this journey and provided me an opportunity to contribute research! science.org/doi/10.1126/sc…

I just updated the scDiffEq Python API (v1.1.0) to include animated visualizations of simulations. You can generate GIFs (or still images) showing: - Temporal gene expression dynamics - UMAP projections of simulated trajectories During my PhD, I found animations like these useful in presentations. Available now in the latest release: scdiffeq.com/_tutorials/vis…

Our review on cell cycle – cell fate (de)coupling is out! doi.org/10.1242/dev.20… Was a lot of fun writing this with @KleinLabHMS , reading old papers (earliest frm 1902) & speculating why cell cycle progression is nt necessary for differentiation across many tissues & species.

Using PBS-M is simple and could enable or improve scRNA-seq for most marine organisms. We hope it's useful for people studying a variety of animals, allowing researchers to better explore the diversity of cell types across marine species 7/7

The PBS-M data also reveals some cells which are otherwise under-represented or absent. These may represent cells which are particularly sensitive to osmotic shock, and we can't detect these cells in scRNA-seq without using PBS-M! 6/7

scRNA-seq is great for non-model organisms—with just a transcriptome you can discover new cell types. But for many marine organisms there's one big problem: SALT 🧂 A solution from our awesome student Tal Scully (1/7🧵) biorxiv.org/content/10.110…

Shout out to @Nich, @jgungabeesoon, @Mate_Kiss on our paper doi.org/10.1016/j.cell… on heterogeneity in tumor neutrophils and why it matters. A great summary by @PittetLab below:

❔What is special about an immune system that successfully attacks tumors, compared to one that doesn’t? Our new study in @CellCellPress led by @jgungabeesoon, @Nich and @Mate_Kiss_ aimed to address this question. A joint work with the great @KleinLabHMS authors.elsevier.com/a/1gqieL7PXmbtw

This is a fabulous collaboration between @KleinLabHMS and @ShouwenW, @Li_Li_666, and @FD_Camargo. The DARLIN mice is superior to CARLIN, and the single-cell multi-omic lineage tracing method is a great addition to single-cell genomics toolkits!

It has been great to have @ShouwenW in our lab. Huge congratulations for starting his own lab at @Westlake_Uni ! Looking forward to more awesome work from your lab!

Very pleased to share work from @KalkiKukreja @kb_mccauley with @jaffeab studying the plasticity of cell and tissue phenotypes under stimulation of 17 different signaling pathways. How “canalized” is cell differentiation? Can we identify the signals inducing disease states?

Interested to learn abt single-cell genomics research in India? Join @Sci_ROI's webinar on prospects and challenges of employing sc-omics in India. July 23rd (Saturday) 10 am to 12:15 pm EDT More info and registration link here: sciroi.net/event/challeng… RT n spread the word 🙏

Congrats Shou-Wen for your next move @Westlake_Uni ! Also, please check out the CoSpar video if you are interested!