Dec 2, 2019

10 Things to Know About the Chromium Single Cell ATAC Solution

Olivia Habern

We may have already given away the first thing that we want you to know about the Chromium Single Cell ATAC (Assay for Transposase Accessible Chromatin) Solution, but we’re grateful and honored to share that…

1. The Chromium Single Cell ATAC Solution has been named among the Top 10 Innovations of 2019, according to the annual ranking conducted by The Scientist.

This is a prestigious award that seeks to identify newly released products with a big impact on life-science research. You can learn more about this award, and read the article announcing the full list of winners for 2019.

And you can keep reading this article to learn 9 more things about our single cell, genome-wide chromatin profiling technology.

**2. How does it work? **

The Chromium Single Cell ATAC Solution gives scientists a window into the regulatory landscape controlling gene expression in individual cells. A transposase enzyme is used to tag accessible regions of chromatin with adaptors. These regions are sequenced, and can be used to infer and map transcription factor binding sites, among other regulatory structures, and to build gene regulatory networks.

Take a look at this How It Works video to get a better understanding of the Chromium Single Cell ATAC Solution:

**3. How to Get Started with the Chromium Single Cell ATAC Solution **

It’s one thing to know how a product or assay works, but another thing entirely to know what kind of information you can gain from it, how it can help address your research questions, and how you can begin using it.

Laura DeMare, Ph.D., and Associate Product Manager of Epigenomics at 10x Genomics, gives an overview of the Chromium Single Cell ATAC Solution in this on-demand webinar. Explore the experimental workflow and data analysis pipeline, and get some helpful recommendations for sample preparation.

Watch here →

4. How to Integrate Single Cell ATAC-seq Data with Other Data Types for Multiomic Analysis

Many 10x customers have asked us how they can integrate single cell ATAC-seq data with other data types, including transcriptomic data, to get a more complete profile of each cell type and its function. Dr. Rahul Satija, Core Faculty Member at the New York Genome Center, and his research team developed a software called Seurat that enables single cell data integration. Explore the capabilities of Seurat in this webinar →

You can also read our recent blog post, summarizing the answers to common Q&A questions. Read here → 

Speaking of 10x customers… The Chromium Single Cell ATAC Solution has been used by a number of scientists to make important discoveries across diverse research areas, including immuno-oncology, developmental biology, and cell atlas studies.

5. ATAC-seq Reveals Chromatin Regulators of T Cell Response to Checkpoint Blockade

Researchers from Stanford University used single cell ATAC-seq to characterize the chromatin regulators of therapy-responsive intratumoral T cells after PD-1 blockade in patients with basal cell carcinoma (1). Their work is helping to resolve some of the complex biology underlying the variable patient response to immunotherapies, which is one of the biggest questions of cancer research today.

Review the paper, and read our blog post to learn more about this discovery.

**6. Researchers Map the Complex Regulatory Landscape of Mixed Phenotype Acute Leukemia **

Granja et al. studied the transcriptional and chromatin signatures of a set of mixed phenotype acute leukemia (MPAL) clinical samples, seeking to identify molecular drivers of malignancy that are consistent between cell types from different hematopoietic lineages. Using single cell ATAC-seq, they characterized 91,601 putative gene-regulatory interactions and several transcription factors that may regulate leukemia genes (2). Their work uniquely links the study of malignancy with developmental biology and explores the role of transcription regulation in driving the cell fate towards cancer.

Review their abstract, and watch Dr. William Greenleaf, Associate Professor in the Department of Genetics at Stanford University, and corresponding author, speak on the findings from this paper in an on-demand webinar, “Identifying Cancer Signatures with Single Cell Multiomics”.

Watch here →

**7. Chromatin Profiling Uncovers the Regulators of Epithelial Cell Identity  **

A team of researchers from UC Irvine used single cell RNA-seq and ATAC-seq to characterize the cell types that compose the mouse mammary epithelial cell system. They identified novel differentiation states in the secretory type of luminal cells and novel cis- and _trans-_regulatory elements in other epithelial cell types (3). Their work demonstrates the power of integrating transcriptome and chromatin profiling to understand what defines unique cell types and states, and how these states may arise in diseases of the mammary epithelial tissue.

Read more about their research here →

8. ATAC-Seq Shows that Epigenetic Adaptations Make Some Retinal Cells Live Longer than Others

Researchers from Baylor College of Medicine studied retinal degeneration in mice to understand why some genetically identical cells survive longer than others over the duration of neurodegenerative diseases. Using single cell RNA-seq and ATAC-seq, they found that surviving cells acquire a transcriptome profile achieved by modulation of the epigenome and changes of the chromatin state. Their work shows that cells can adapt to genetic stress induced by disease through epigenetic regulation (4).

Read more about this discovery →

**9. ATAC-Seq Allows Researchers to Explore Cell Type-Specific HOX Factor Activity **

Scientists from the Montreal Clinical Research Institute used single cell ATAC-seq to study tissue-specific HOX transcription factor binding activity. They observed that HOX13 factors initiate development of distal limbs by triggering chromatin opening. However, access to single cell resolution data enabled them to see that the HOX factors promote chromatin opening at specific points in the differentiation trajectory of distal cell types (5).

Explore their abstract →

Now, last but not least…

10. The People Behind the Product

The Chromium Single Cell ATAC Solution has been supported by a talented group of scientists, engineers and product marketers, all of whom are working behind the scenes to ensure this technology continues to meet the needs of 10x Genomics customers. Get to know some of the team members and their thoughts on the ATAC solution:

Corey Nemec, Scientist II

Corey Nemec
Corey Nemec

How have you supported the ATAC solution?

“I've been working in R&D on our Single Cell ATAC Solution for nearly two years. I was involved with initial assay development, optimization, product validation, and the transition to our Next GEM technology.”

What do you want to tell the world about this solution?

“Multiple assays exist to interrogate the epigenome, including MNase-seq, DNase-seq, FAIRE-seq, and ChIP-seq. However, these assays are often laborious, requiring extensive optimization by the users, and single cell end-to-end solutions are not available. The Chromium Single Cell ATAC Solution can capture information overlapping all these techniques at the single cell level and enable users to gain a broad understanding of the epigenome.”

Laura DeMare, Associate Product Manager

How have you supported the ATAC solution?

Laura DeMare
Laura DeMare

“I’m the product manager, so I help scientists understand how single cell ATAC-seq can elevate their research to answer questions not previously accessible by more traditional methods.”

What do you want to tell the world about this solution?

“Profiling chromatin landscapes at the single cell level is a powerful tool for understanding the ‘how’ behind gene expression differences… By layering on regulatory elements and transcription factor activity to RNA-seq data, scATAC-seq can help construct gene regulatory networks and identify potential avenues for targeted treatments or for answering fundamental questions in development, neuroscience, immunology and oncology.

And, by inferring binding sites for hundreds of transcription factors in a single experiment, scATAC-seq is a huge improvement in scale compared to ChIP-seq approaches. Plus, at the resolution of single cells, you can uncover epigenetic insights in rare cell types or states which can be difficult to do.”

Li Wang, Computational Biologist II

How have you supported the ATAC solution?

Li Wang
Li Wang

"I’m a computational biologist and I helped build the Cell Ranger ATAC computational pipeline and application notes for the ATAC solution."

What do you want to tell the world about this solution?

"The epigenome is the hub of gene expression regulation. Profiling the epigenome with single cell ATAC-seq enables dissection of gene expression regulation in complex systems.

_With the Chromium Single Cell ATAC Solution and the computational tools we and others built, researchers can gain deep insights into the mechanisms of epigenetic regulation, transcription factor networks, the interaction between epigenome and transcriptome in cellular state transitions, and so much more." _

Thank you once again to The Scientist and their collaborators for choosing the Chromium Single Cell ATAC Solution as one of the Top 10 Innovations of 2019!

  1. Satpathy A et al., Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat Biotechnol. 37, 925-936. (2019).
  2. Granja J et al., Single-cell multiomic analysis identifies regulatory programs in mixed-phenotype acute leukemia. *Nat Biotechnol. *(2019).
  3. Pervolarakis N et al., Integrated single-cell transcriptomics and chromatin accessibility analysis reveals novel regulators of mammary epithelial cell identity. bioRxiv. (2019).
  4. Dharmat R et al., Epigenetic adaptation prolongs photoreceptor survival during retinal degeneration. bioRxiv. (2019).
  5. Desanlis I et al., HOX13-dependent chromatin accessibility modulates the target repertoires of the HOX factors. bioRxiv. (2019).