A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells

Innate lymphoid cells (ILCs) play important roles in tissue homeostasis and host defense, but the proliferative properties and migratory behavior of especially human ILCs remain poorly understood. Here we mapped at single-cell resolution the spatial distribution of quiescent and proliferative human...

Full description

Bibliographic Details
Main Authors: Yu Gao, Arlisa Alisjahbana, Daryl Zhong Hao Boey, Imran Mohammad, Natalie Sleiers, Joakim S. Dahlin, Tim Willinger
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.902881/full
_version_ 1811312713966551040
author Yu Gao
Arlisa Alisjahbana
Daryl Zhong Hao Boey
Imran Mohammad
Natalie Sleiers
Joakim S. Dahlin
Tim Willinger
author_facet Yu Gao
Arlisa Alisjahbana
Daryl Zhong Hao Boey
Imran Mohammad
Natalie Sleiers
Joakim S. Dahlin
Tim Willinger
author_sort Yu Gao
collection DOAJ
description Innate lymphoid cells (ILCs) play important roles in tissue homeostasis and host defense, but the proliferative properties and migratory behavior of especially human ILCs remain poorly understood. Here we mapped at single-cell resolution the spatial distribution of quiescent and proliferative human ILCs within the vascular versus tissue compartment. For this purpose, we employed MISTRG humanized mice as an in-vivo model to study human ILCs. We uncovered subset-specific differences in the proliferative status between vascular and tissue ILCs within lymphoid and non-lymphoid organs. We also identified CD117-CRTH2-CD45RA+ ILCs in the spleen that were highly proliferative and expressed the transcription factor TCF-1. These proliferative ILCs were present during the neonatal period in human blood and emerged early during population of the human ILC compartment in MISTRG mice transplanted with human hematopoietic stem and progenitor cells (HSPCs). Single-cell RNA-sequencing combined with intravascular cell labeling suggested that proliferative ILCs actively migrated from the local vasculature into the spleen tissue. Collectively, our comprehensive map reveals the proliferative topography of human ILCs, linking cell migration and spatial compartmentalization with cell division.
first_indexed 2024-04-13T10:41:30Z
format Article
id doaj.art-92b31eda76d3420e9350de4cd89f11b5
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-13T10:41:30Z
publishDate 2022-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-92b31eda76d3420e9350de4cd89f11b52022-12-22T02:49:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.902881902881A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cellsYu Gao0Arlisa Alisjahbana1Daryl Zhong Hao Boey2Imran Mohammad3Natalie Sleiers4Joakim S. Dahlin5Tim Willinger6Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenInnate lymphoid cells (ILCs) play important roles in tissue homeostasis and host defense, but the proliferative properties and migratory behavior of especially human ILCs remain poorly understood. Here we mapped at single-cell resolution the spatial distribution of quiescent and proliferative human ILCs within the vascular versus tissue compartment. For this purpose, we employed MISTRG humanized mice as an in-vivo model to study human ILCs. We uncovered subset-specific differences in the proliferative status between vascular and tissue ILCs within lymphoid and non-lymphoid organs. We also identified CD117-CRTH2-CD45RA+ ILCs in the spleen that were highly proliferative and expressed the transcription factor TCF-1. These proliferative ILCs were present during the neonatal period in human blood and emerged early during population of the human ILC compartment in MISTRG mice transplanted with human hematopoietic stem and progenitor cells (HSPCs). Single-cell RNA-sequencing combined with intravascular cell labeling suggested that proliferative ILCs actively migrated from the local vasculature into the spleen tissue. Collectively, our comprehensive map reveals the proliferative topography of human ILCs, linking cell migration and spatial compartmentalization with cell division.https://www.frontiersin.org/articles/10.3389/fimmu.2022.902881/fullinnate lymphoid cellsproliferationmigrationtissue residencyontogenyspleen
spellingShingle Yu Gao
Arlisa Alisjahbana
Daryl Zhong Hao Boey
Imran Mohammad
Natalie Sleiers
Joakim S. Dahlin
Tim Willinger
A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
Frontiers in Immunology
innate lymphoid cells
proliferation
migration
tissue residency
ontogeny
spleen
title A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
title_full A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
title_fullStr A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
title_full_unstemmed A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
title_short A single-cell map of vascular and tissue lymphocytes identifies proliferative TCF-1+ human innate lymphoid cells
title_sort single cell map of vascular and tissue lymphocytes identifies proliferative tcf 1 human innate lymphoid cells
topic innate lymphoid cells
proliferation
migration
tissue residency
ontogeny
spleen
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.902881/full
work_keys_str_mv AT yugao asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT arlisaalisjahbana asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT darylzhonghaoboey asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT imranmohammad asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT nataliesleiers asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT joakimsdahlin asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT timwillinger asinglecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT yugao singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT arlisaalisjahbana singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT darylzhonghaoboey singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT imranmohammad singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT nataliesleiers singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT joakimsdahlin singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells
AT timwillinger singlecellmapofvascularandtissuelymphocytesidentifiesproliferativetcf1humaninnatelymphoidcells