Journal article

Single-cell transcriptomics of alloreactive CD4( ) T cells over time reveals divergent fates during gut graft-versus-host disease

Jessica A Engel, Hyun Jae Lee, Cameron G Williams, Rachel Kuns, Stuart Olver, Lianne IM Lansink, Megan SF Soon, Stacey B Andersen, Joseph E Powell, Valentine Svensson, Sarah A Teichmann, Geoffrey R Hill, Antiopi Varelias, Motoko Koyama, Ashraful Haque

JCI INSIGHT | AMER SOC CLINICAL INVESTIGATION INC | Published : 2020

Abstract

Acute gastrointestinal (GI) graft-versus-host disease (GVHD) is a primary determinant of mortality after allogeneic hematopoietic stem cell transplantation (alloSCT). The condition is mediated by alloreactive donor CD4+ T cells that differentiate into pathogenic subsets expressing IFN-γ, IL-17A, or GM-CSF and is regulated by subsets expressing IL-10 and/or Foxp3. Developmental relationships between Th cell states during priming in mesenteric lymph nodes (mLNs) and effector function in the GI tract remain undefined at genome scale. We applied scRNA-Seq and computational modeling to a mouse model of donor DC-mediated GVHD exacerbation, creating an atlas of putative CD4+ T cell differentiation ..

View full abstract

Grants

Awarded by Australian National Health and Medical Research Council



Funding Acknowledgements

This work was supported by research grants from the Australian National Health and Medical Research Council: AH, SAT, and MK were supported by Project and Ideas Grants (1126399 and 1180951). JEP is supported by an Investigator Grant (1175781). We would like to thank staff from the QIMR Berghofer flow cytometry facility for their expertise and assistance with experiments, and staff from QIMR Berghofer animal facility for animal care and husbandry. We acknowledge Paul Collins at the QIMR Berghofer sequencing facility and Scott Wood and his team at the QIMR Berghofer High Performance Computing facility for support with scRNA-Seq data management. We acknowledge helpful discussions with Kate Gartlan (QIMR Berghofer) on matters relating to T cell differentiation during alloSCT. We thank Kylie R. James (Wellcome Sanger Institute) for reading the manuscript and providing helpful comments on issues relating to CD4+ T cell differentiation. We acknowledge BGI Australia for their help in sequencing of 10x libraries on the MGISEQ-2000, especially Lynn Fink, Cheryll Ye, Shiu Wing In, Ivon Harliwong, Tian Wei, and Wei Han Min for their role in assisting with 10x library conversion, pooling design, sequencing and demultiplexing of data