Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

Sonya A. MacParland; Jeff C. Liu; Xue Zhong Ma; Brendan T. Innes; Agata M. Bartczak; Blair K. Gage; Justin Manuel; Nicholas Khuu; Juan Echeverri; Ivan Linares; Rahul Gupta; Michael L. Cheng; Lewis Y. Liu; Damra Camat; Sai W. Chung; Rebecca K. Seliga; Zigong Shao; Elizabeth Lee; Shinichiro Ogawa; Mina Ogawa; Michael D. Wilson; Jason E. Fish; Markus Selzner; Anand Ghanekar; David Grant; Paul Greig; Gonzalo Sapisochin; Nazia Selzner; Neil Winegarden; Oyedele Adeyi; Gordon Keller; Gary D. Bader; Ian D. McGilvray

doi:10.1038/s41467-018-06318-7

Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

Sonya A. MacParland, Jeff C. Liu, Xue Zhong Ma, Brendan T. Innes, Agata M. Bartczak, Blair K. Gage, Justin Manuel, Nicholas Khuu, Juan Echeverri, Ivan Linares, Rahul Gupta, Michael L. Cheng, Lewis Y. Liu, Damra Camat, Sai W. Chung, Rebecca K. Seliga, Zigong Shao, Elizabeth Lee, Shinichiro Ogawa, Mina OgawaMichael D. Wilson, Jason E. Fish, Markus Selzner, Anand Ghanekar, David Grant, Paul Greig, Gonzalo Sapisochin, Nazia Selzner, Neil Winegarden, Oyedele Adeyi, Gordon Keller, Gary D. Bader, Ian D. McGilvray

Laboratory Medicine and Pathology

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Abstract

The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.

Original language	English (US)
Article number	4383
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06318-7
State	Published - Dec 1 2018

Bibliographical note

Funding Information:
This research was funded in part by the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund (CFREF) to IDM and by start-up funds from the Multi-Organ transplant program at the UHN to SAM. We would like to acknowledge Dr. M. Guilliams (VIB, Ghent University) and Dr. I.N. Crispe (University of Washington) for discussions of macrophage ontogeny. We would like to thank Joy Qu [www.joyqu.ca] for generating the illustration in Fig. 10. This work was supported by NRNB (U.S. National Institutes of Health, grant P41 GM103504) to GDB.

Publisher Copyright:
© 2018, The Author(s).

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Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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MacParland, S. A., Liu, J. C., Ma, X. Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., Gupta, R., Cheng, M. L., Liu, L. Y., Camat, D., Chung, S. W., Seliga, R. K., Shao, Z., Lee, E., Ogawa, S., ... McGilvray, I. D. (2018). Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nature communications, 9(1), Article 4383. https://doi.org/10.1038/s41467-018-06318-7

MacParland, SA, Liu, JC, Ma, XZ, Innes, BT, Bartczak, AM, Gage, BK, Manuel, J, Khuu, N, Echeverri, J, Linares, I, Gupta, R, Cheng, ML, Liu, LY, Camat, D, Chung, SW, Seliga, RK, Shao, Z, Lee, E, Ogawa, S, Ogawa, M, Wilson, MD, Fish, JE, Selzner, M, Ghanekar, A, Grant, D, Greig, P, Sapisochin, G, Selzner, N, Winegarden, N, Adeyi, O, Keller, G, Bader, GD & McGilvray, ID 2018, 'Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations', Nature communications, vol. 9, no. 1, 4383. https://doi.org/10.1038/s41467-018-06318-7

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title = "Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations",

abstract = "The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.",

author = "MacParland, {Sonya A.} and Liu, {Jeff C.} and Ma, {Xue Zhong} and Innes, {Brendan T.} and Bartczak, {Agata M.} and Gage, {Blair K.} and Justin Manuel and Nicholas Khuu and Juan Echeverri and Ivan Linares and Rahul Gupta and Cheng, {Michael L.} and Liu, {Lewis Y.} and Damra Camat and Chung, {Sai W.} and Seliga, {Rebecca K.} and Zigong Shao and Elizabeth Lee and Shinichiro Ogawa and Mina Ogawa and Wilson, {Michael D.} and Fish, {Jason E.} and Markus Selzner and Anand Ghanekar and David Grant and Paul Greig and Gonzalo Sapisochin and Nazia Selzner and Neil Winegarden and Oyedele Adeyi and Gordon Keller and Bader, {Gary D.} and McGilvray, {Ian D.}",

note = "Funding Information: This research was funded in part by the University of Toronto{\textquoteright}s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund (CFREF) to IDM and by start-up funds from the Multi-Organ transplant program at the UHN to SAM. We would like to acknowledge Dr. M. Guilliams (VIB, Ghent University) and Dr. I.N. Crispe (University of Washington) for discussions of macrophage ontogeny. We would like to thank Joy Qu [www.joyqu.ca] for generating the illustration in Fig. 10. This work was supported by NRNB (U.S. National Institutes of Health, grant P41 GM103504) to GDB. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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AU - MacParland, Sonya A.

AU - Liu, Jeff C.

AU - Ma, Xue Zhong

AU - Innes, Brendan T.

AU - Bartczak, Agata M.

AU - Gage, Blair K.

AU - Manuel, Justin

AU - Khuu, Nicholas

AU - Echeverri, Juan

AU - Linares, Ivan

AU - Gupta, Rahul

AU - Cheng, Michael L.

AU - Liu, Lewis Y.

AU - Camat, Damra

AU - Chung, Sai W.

AU - Seliga, Rebecca K.

AU - Shao, Zigong

AU - Lee, Elizabeth

AU - Ogawa, Shinichiro

AU - Ogawa, Mina

AU - Wilson, Michael D.

AU - Fish, Jason E.

AU - Selzner, Markus

AU - Ghanekar, Anand

AU - Grant, David

AU - Greig, Paul

AU - Sapisochin, Gonzalo

AU - Selzner, Nazia

AU - Winegarden, Neil

AU - Adeyi, Oyedele

AU - Keller, Gordon

AU - Bader, Gary D.

AU - McGilvray, Ian D.

N1 - Funding Information: This research was funded in part by the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund (CFREF) to IDM and by start-up funds from the Multi-Organ transplant program at the UHN to SAM. We would like to acknowledge Dr. M. Guilliams (VIB, Ghent University) and Dr. I.N. Crispe (University of Washington) for discussions of macrophage ontogeny. We would like to thank Joy Qu [www.joyqu.ca] for generating the illustration in Fig. 10. This work was supported by NRNB (U.S. National Institutes of Health, grant P41 GM103504) to GDB. Publisher Copyright: © 2018, The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.

AB - The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.

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Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

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