title: A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.
abstract: The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.
authors.affiliation: Biomedical Sciences Graduate Program, Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Scoville
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Mundy-Bosse
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Zhang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Keller
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Biomedical Sciences Graduate Program, Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Luxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Biomedical Sciences Graduate Program, Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Bergin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hsiaoyin C
authors.initials: HC
authors.lastname: Mao
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: McClory
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: michael.caligiuri@osumc.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: aharon.freud@osumc.edu.
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002648:Child; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000502:physiology*; D054503:Lymphoid Progenitor Cells / Q000502:physiology*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D014066:Palatine Tonsil / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D017493:Leukocyte Common Antigens