In this overview, we describe the T-ChIC methodology: what it can be used for, how it compares to existing single-cell technologies, and its main advantages and limitations.
What is the name of the methodology?
T-ChIC: a multimodal single-cell method for the detection of whole transcripts and histone modifications in the same cell.
Developed by the Alexander van Oudenaarden group
What is the methodology good for?
T-ChIC provides a highly sensitive and specific read-out of genome-wide chromatin modification distributions in combination with the whole transcriptome of the same cell.
What is/are the main advantages of this methodology over related technologies?
The combination of transcriptome and histone modification enables an easy cell type assignment and integration of multiple histone marks via the shared transcriptome.
Comparing the transcriptional and epigenetic state of a gene can be performed within the same cell rather than between different cells, measured across experiments, thus mitigating the need to use computational integration methods with poorly tractable outcomes.
The technique is FACS-based, and is thus compatible with cell tracer and/or antibody staining, which can provide another layer of information and enables mixing multiple samples in the same plate, mitigating the technical effects of sorting.
What are the most important limitations of the methodology?
A plate-based experimental setup requires nanoliter-volume pipetting robots. It also limits the throughput to only a few thousand cells per week. Bioinformatic skills are a prerequisite for analyzing the sequencing results.
What type of samples are compatible with methodology (yes, no, possibly)?
Cancer cell lines | Primary cells in culture | Organoids | Primary tissue |
Yes | Yes | Yes | Yes |
If someone outside your lab wants to use the methodology, what is the best option?
Because nanoliter-volume pipetting robots are a prerequisite for the experiment, the most straightforward option would be to contact the Single Cell Core, which provides technologies developed by our group to the broader scientific community. Practically, you would provide them with (fixed) cells, and they would perform the experiment for you, returning demultiplexed bam files and count tables.
Direct collaborations with our group are also possible in a similar setup.
Name one or more people in your lab that are experienced with the methodology
Alberto Griffa
Widad Mâmmer Bouhou (at the Single Cell Core)
Who originally developed the methodology?
Peter Zeller and others in the van Oudenaarden Group originally developed the technique. Pre-print is available at https://doi.org/10.1101/2024.05.09.593364.
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