Spatial-CITE-seq: spatially resolved high-plex protein and whole transcriptome co-mapping

Abstract

We present spatial-CITE-seq for high-plex protein and whole transcriptome co-mapping, which was firstly demonstrated for profiling 189 proteins and transcriptome in multiple mouse tissue types. It was then applied to human tissues to measure 273 proteins and transcriptome that revealed spatially distinct germinal center reaction in tonsil and early immune activation in skin at the COVID-19 mRNA vaccine injection site. Spatial-CITE-seq may find a range of applications in biomedical research.

Spatial transcriptomics using multiplexed deterministic barcoding in tissue

“…Furthermore, barcoding strategies with microfluidic channels can be combined with a multitude of modalities, including DNA-barcoded antibodies 17 , chromatin accessibility 19 , and epigenomic readouts 18 . To increase adaptability, xDBiT libraries can be sequenced using standard next generation sequencing platforms.…”

“…Deterministic barcoding in tissue (DBiT-seq) is a cost-effective and openly accessible platform to scale ST 16 . DBiT-seq uses microfluidic channels to barcode tissue sections using DNA oligonucleotides and allows the integration of multi-omics information, including antibodies 17 , epigenomics 18 , and chromatin accessibility readouts 19 .…”

The 3D genome landscape: Diverse chromosomal interactions and their functional implications

“…High-throughput imaging technologies have shown significant strides in bridging the gap from single cells to multicellular tissues using spatial genomics and transcriptomics ( Kempfer and Pombo, 2020 ; Jerkovic and Cavalli, 2021 ; Rao et al, 2021 ; Zhao et al, 2022 ). Spatial-based DNA and RNA approaches integrated with burgeoning multiplexed protein imaging ( Hickey et al, 2021 ; Takei et al, 2021 ; Ben-Chetrit et al, 2022 ; Liu et al, 2022 ; Vickovic et al, 2022 ) will enhance the understanding of how the dynamics of genome organization and function contribute to cellular identities.…”

Unbiased spatial proteomics with single-cell resolution in tissues

“…Cyclic immunofluorescence (CyCIF), ChipCytometry (Canopy Biosciences), Cell DIVE (Leica), co-detection by indexing (CODEX, Akoya Biosciences), GeoMx DSP (nanoString), immunostaining with signal amplification by exchange reaction (immuno-SABER), multiplexed ion beam imaging by time of flight (MIBI-TOF), imaging mass cytometry (IMC), deep visual proteomics (DVP), nanodroplet processing in one pot for trace samples (nanoPOTS), matrix-assisted laser desorption/ionization (MALDI), single-cell proteomics (SCP) (Brunner et al, 2022;Budnik et al, 2018;Hickey et al, 2021;Jarosch et al, 2021;Mund et al, 2022). Spatial-CITE-seq utilizes spatial barcoding and high-throughput sequencing for protein mapping with cellular resolution (Liu et al, 2022).…”

“…Hence, acquiring spatial multi-omics profiles may enable the reconstruction of key processes of tumorigenesis in a holistic manner. For example, a new technology called spatial-CITEseq (spatial co-indexing of transcriptomes and epitopes) combines next-generation sequencing with antibody-based tissue barcoding to map 300 proteins and the whole transcriptome (Liu et al, 2022). Another example is spatial-CUT&Tag that combines microfluidic deterministic barcoding, next-generation sequencing, and imaging to spatially resolve single-cell epigenome profiling in frozen tissue (Deng et al, 2022).…”