Delighted to share new work from our lab: MultiPerturb-seq 🎛️ ❌ ↕️ Over the last few years, we've been combining CRISPR screens with multimodal readouts of gene expression (RNA) and chromatin accessibility (DNA). In this study, we bring those together within the same cells. - ThreadSky

nevillesanjana.bsky.social • 121 days ago

Delighted to share new work from our lab:
MultiPerturb-seq 🎛️ ❌ ↕️

Over the last few years, we've been combining CRISPR screens with multimodal readouts of gene expression (RNA) and chromatin accessibility (DNA). In this study, we bring those together within the same cells.

Reposted from Nature Biotechnology

Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling go.nature.com/4hXER5O

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nevillesanjana.bsky.social•121 days ago

First, huge shout-out to superstar MD-PhD student #RachelYan who led this project from start to finish. Rachel was motivated to build MultiPerturb-seq to search for new cancer therapies for rare pediatric brain tumors 🧠👩‍⚕️💊
But first you need to know how MPS works.

nevillesanjana.bsky.social•121 days ago

MPS links pooled CRISPR genetic perturbations — in our case, knockdown via CRISPRi but could also be knock-out or activation — with single-cell open chromatin (ATAC-seq) and gene expression (RNA-seq) profiles at scale.

nevillesanjana.bsky.social•121 days ago

In MultiPerturb-seq, we combine combinatorial indexing and droplet microfluidics to scale throughput — loading 100,000 cells on a single 10X Chromium ATAC lane.

nevillesanjana.bsky.social•121 days ago

This results in significant cost advantages over existing uni- and multimodal single-cell perturbation approaches.

nevillesanjana.bsky.social•121 days ago

Now, onto the biology! While we’ve made incredible progress in treating a number of cancers, most are still difficult to treat. In cancers such as atypical teratoid/rhabdoid tumor (AT/RT), outcomes remain poor despite intensive treatment regimens, e.g.:
https://doi.org/10.1200/JCO.19.01776

nevillesanjana.bsky.social•121 days ago

AT/RT is itself a disease of chromatin and gene expression: It is driven by biallelic loss of SMARCB1 — an essential subunit of the SWI/SNF chromatin remodeling complex. This loss arrests progenitor differentiation and fuels tumor proliferation.

psmibert.bsky.social•120 days ago

Lovely work Neville and team. Congrats!

rnadoctor.bsky.social•119 days ago

Congratulations, Neville! Amazing work! Also, I am now following you here on @bsky.app. I am trying to move away from X as it is no longer a safe space for scientists.

lucksmith.bsky.social•119 days ago

exciting technology! congrats to the sanjana team.

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