{"id":118816,"date":"2025-08-29T16:39:13","date_gmt":"2025-08-29T16:39:13","guid":{"rendered":"https:\/\/www.newsbeep.com\/us\/118816\/"},"modified":"2025-08-29T16:39:13","modified_gmt":"2025-08-29T16:39:13","slug":"bgi-research-publishes-stereo-seq-v2-unlocking-high-resolution-in-situ-host-microbe-transcriptome-mapping-on-ffpe-samples","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/us\/118816\/","title":{"rendered":"BGI-Research Publishes Stereo-Seq V2: Unlocking High-Resolution, In Situ Host\u2013Microbe Transcriptome Mapping On FFPE Samples"},"content":{"rendered":"

<\/p>\n

Formalin-fixed,
\nparaffin-embedded (FFPE) tissues represent the predominant sample conservation
\nmethod in clinical practice, yet degraded and crosslinked RNA has long limited
\nwhole-transcriptome analysis and spatial context. <\/p>\n

On
\nAugust 28, in Cell, researchers
\nat BGI-Research and collaborating clinical and
\nresearch centers published Stereo-seq V2, a spatial transcriptomics method that
\nachieves single-cell\u2013level resolution on FFPE sections and, critically, enables
\nsimultaneous in situ profiling of host and microbial RNAs. By combining
\ndeparaffinization\/decrosslinking with random-primed capture and uniform
\ngene-body coverage, Stereo-seq V2 opens FFPE “black boxes” for
\ninfectious disease biology, tumor ecosystems, and clinical research applications.<\/p>\n

<\/p>\n

The study \u201cStereo-seq V2: Spatial
\nmapping of total RNA on FFPE sections with high resolution\u201d was published in
\nCell.<\/p>\n

\"Title:
Stereo-seq V2 workflow enables simultaneous host and microbial RNA mapping
\non FFPE tissues with single-cell resolution.<\/p>\n

Built
\non the large field of view and subcellular spot spacing of Stereo-seq, the V2
\nchemistry replaces poly(T) capture with random primers, increasing sensitivity
\nto low-abundance and non-poly(A) RNAs while maintaining signal-to-noise. This
\nadvance enables sharper boundaries and cellular resolution, with V2 reducing
\nlateral diffusion at tissue borders and achieving true single-cell segmentation on FFPE sections, identifying 34 cell
\ntypes in mouse brain. Across adjacent mouse brain sections, V2 and V1 showed
\nhigh concordance in gene expression and reduced apparent lateral diffusion at
\nanatomical borders. <\/p>\n

Compared
\nwith existing probe-based methods, V2 provides whole-transcriptome coverage,
\nsignificantly expanding beyond traditional probe limitations, while recovering
\nimportant markers and regulatory genes otherwise missed or inconsistently
\ncaptured by probe panels. Uniform coverage across exons improves detection of
\ntranscription factors, adhesion genes, and alternative splicing events,
\ncategories that often prove elusive with 3\u2032-biased strategies.<\/p>\n


Stereo-seq V2 demonstrates improved spatial resolution with reduced lateral
\ndiffusion at tissue boundaries and achieves single-cell resolution on FFPE
\nsections, identifying 34 distinct cell types in mouse brain.<\/p>\n

Demonstrating
\nclinical FFPE robustness, V2 maintains high gene capture even on severely
\ndegraded samples and aligns molecular signatures with histological features
\nlike necrosis. V2 performs robustly on clinical FFPE samples with poor RNA
\nintegrity. In a cohort of triple-negative breast cancer (TNBC) blocks preserved
\nfrom under 1 to ~9 years, V2 maintained consistent gene capture. The method
\nshowed reliable performance across different tissue conditions. <\/p>\n

Spatial
\nexpression recapitulated clinical immunohistochemical phenotypes (e.g., low
\nESR1\/PGR\/ERBB2), delineated malignant, immune, and necrotic regions, and
\nsupported tumor subtype classification through genetic analysis. Whole
\ngene-body coverage enabled spatial alternative splicing analysis, identifying
\n1,492 events including specific splicing patterns in tumor-associated genes
\nlike ZNF226, GIPC1, and BEX4 that varied between tumor subtypes. These findings
\nadd molecular granularity to tumor biology beyond expression alone.<\/p>\n

\"Title:
V2 maintains robust gene capture across degraded clinical TNBC samples and
\naccurately maps tumor, immune, and necrotic regions.<\/p>\n

A
\ncore advantage is unbiased, concurrent
\nmapping of host and microbial RNAs directly on FFPE tissue, enabling
\nhost\u2013microbe battlefield mapping where V2 simultaneously maps spatial B-cell
\nreceptor (BCR) clones in human Tuberculosis (TB)
\nlungs and tracks Mtb infection dynamics with bacterial RNA peaking at 4 weeks
\nin mouse models. <\/p>\n

In
\na Mycobacterium tuberculosis (Mtb) mouse model profiled at 1 day, 4 weeks, and
\n8 weeks post infection, V2 captured the rise-and-fall kinetics of bacterial
\ntranscripts consistent with histology and CFU counts and identified host gene
\nmodules spatially correlated with Mtb burden, shifting from inflammatory and
\ncell death pathways to adaptive immunity over time. <\/p>\n

Stereo-seq
\nV2 further resolves the in situ BCR repertoire. Compared with
\npoly(A)-based methods, V2 provides markedly improved coverage of V regions,
\nenabling assembly of clonotypes and analysis of somatic hypermutation. The
\nnumber of assembled BCR clones increased from 185 at 4 weeks to 1,736 at 8 weeks,
\nwith greater clonal diversity and mutation frequency proximal to infected
\nregions, consistent with affinity maturation. <\/p>\n

In
\nhuman TB FFPE lung samples, V2 similarly mapped host and pathogen RNAs,
\ndelineated necrotic boundaries from RNA density, and revealed recurrent BCR
\nclones across patients; related clones were enriched in blood from active TB
\ncases, pointing to potential diagnostic and therapeutic targets.<\/p>\n


Spatial BCR repertoire analysis reveals clonal expansion and affinity
\nmaturation in TB-infected tissues, with related clones detected in patient
\nblood.<\/p>\n

Together,
\nthese results position Stereo-seq V2 as a broadly applicable platform for
\nsingle-cell\u2013level, whole-transcriptome mapping on FFPE sections, extending
\nspatial transcriptomics to the most abundant and clinically relevant specimens.
\nBy unifying host gene programs, immune repertoires, and pathogen localization
\nwithin the same section, V2 provides a panoramic readout of tissue ecosystems
\nin cancer, infection, and beyond, and may accelerate retrospective biomarker
\ndiscovery, mechanism-based stratification, and antibody or vaccine development
\nusing existing archives.<\/p>\n

All
\nhuman and animal studies were conducted with appropriate institutional ethics
\napprovals and followed established guidelines for research involving clinical
\nspecimens and laboratory animals. Data and code availability: Raw data are
\ndeposited in the Genome Sequence Archive; analysis code is available at the
\nproject repository: GitHub (Stereo-seq V2 code) at https:\/\/github.com\/YoungLi88\/Stereo-seq-V2<\/a>. The study can be accessed here: https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00922-5?rss=yes<\/a> <\/p>\n<\/p>\n<\/p>\n<\/p>\n<\/p><\/p>\n","protected":false},"excerpt":{"rendered":"Formalin-fixed, paraffin-embedded (FFPE) tissues represent the predominant sample conservation method in clinical practice, yet degraded and crosslinked RNA…\n","protected":false},"author":2,"featured_media":118817,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[50],"tags":[200,79],"class_list":["post-118816","post","type-post","status-publish","format-standard","has-post-thumbnail","category-genetics","tag-genetics","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/118816","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/comments?post=118816"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/118816\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media\/118817"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media?parent=118816"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/categories?post=118816"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/tags?post=118816"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}