Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143904" target="_blank" >RIV/00216224:14740/25:00143904 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1013682" target="_blank" >https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1013682</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pcbi.1013682" target="_blank" >10.1371/journal.pcbi.1013682</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs

Popis výsledku v původním jazyce

Single-cell RNA sequencing (scRNA-Seq) provides valuable insights into cell biology. However, current scRNA-Seq analytic approaches do not distinguish between spliced and unspliced mRNA at the level of dimensionality reduction. RNA velocity paradigms suggest that the presence of unspliced mRNA reflects transitional cell states, informative for studies of dynamic processes such as embryogenesis or tissue regeneration. Alternatively, stable cell subsets may also maintain translationally repressed spliced mRNA in processing bodies (P-bodies) and/or unspliced mRNA reservoirs for prompt initiation of transcription-independent expression. To enable splicing-aware analysis of scRNA-Seq data, we developed a method called SANSARA (Splicing-Aware scrNa-Seq AppRoAch). We employed SANSARA to characterize peripheral blood regulatory T cell (Treg) subsets, revealing a complementary interplay between the FoxP3 and Helios master transcription factors and upregulation of functionally relevant IL10RA, LGALS3, FCRL3, CD38, ITGAL, and LEF1 spliced gene forms in effector Tregs. Among Th1 and cytotoxic CD4+ T cell subsets, SANSARA also revealed substantial splicing heterogeneity across subset-specific genes. SANSARA is straightforward to implement in current data analysis pipelines and opens new dimensions for scRNA-Seq-based discoveries.

Název v anglickém jazyce

Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs

Popis výsledku anglicky

Single-cell RNA sequencing (scRNA-Seq) provides valuable insights into cell biology. However, current scRNA-Seq analytic approaches do not distinguish between spliced and unspliced mRNA at the level of dimensionality reduction. RNA velocity paradigms suggest that the presence of unspliced mRNA reflects transitional cell states, informative for studies of dynamic processes such as embryogenesis or tissue regeneration. Alternatively, stable cell subsets may also maintain translationally repressed spliced mRNA in processing bodies (P-bodies) and/or unspliced mRNA reservoirs for prompt initiation of transcription-independent expression. To enable splicing-aware analysis of scRNA-Seq data, we developed a method called SANSARA (Splicing-Aware scrNa-Seq AppRoAch). We employed SANSARA to characterize peripheral blood regulatory T cell (Treg) subsets, revealing a complementary interplay between the FoxP3 and Helios master transcription factors and upregulation of functionally relevant IL10RA, LGALS3, FCRL3, CD38, ITGAL, and LEF1 spliced gene forms in effector Tregs. Among Th1 and cytotoxic CD4+ T cell subsets, SANSARA also revealed substantial splicing heterogeneity across subset-specific genes. SANSARA is straightforward to implement in current data analysis pipelines and opens new dimensions for scRNA-Seq-based discoveries.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Plos Computational Biology

ISSN

1553-734X

e-ISSN

1553-7358

Svazek periodika

21

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1-17

Kód UT WoS článku

001611256300002

EID výsledku v databázi Scopus

2-s2.0-105023069535