Single‐Cell, Single‐Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity
Name
Hepatology Communications - 2021 - Andrews - Single‐Cell Single‐Nucleus and Spatial RNA Sequencing of the Human Liver.pdf
Description
Published version
Size
3.49 MB
Format
Adobe PDF
Checksum (MD5)
1368520955516fd23e5ac75825946279
Author(s)
Andrews, Tallulah S
Atif, Jawairia
Liu, Jeff C
Perciani, Catia T
Ma, Xue-Zhong
Thoeni, Cornelia
Slyper, Michal
Eraslan, Gökcen
Segerstolpe, Asa
Manuel, Justin
Date Issued
2022
Journal
Hepatology Communications
Publisher
Wiley
Citation
Andrews, Tallulah S, Atif, Jawairia, Liu, Jeff C, Perciani, Catia T, Ma, Xue-Zhong et al. 2022. "Single‐Cell, Single‐Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity." Hepatology Communications, 6 (4).
Version
Final published version
Abstract
The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation-related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at a single-cell resolution, revealed the presence of rare subtypes of liver mesenchymal cells, and facilitated the detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and natural killer cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte, and mesenchymal cell populations by an independent spatial transcriptomics data set and immunohistochemistry. Conclusion: Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/HEP4.1854
