Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus

TY - JOUR

T1 - Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus

AU - Ulyanchenko, Svetlana

AU - O'Neill, Kathy E

AU - Medley, Tanya

AU - Farley, Alison M

AU - Vaidya, Harsh J

AU - Cook, Alistair M

AU - Blair, Natalie F

AU - Blackburn, C Clare

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/3/29

Y1 - 2016/3/29

N2 - Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam+UEA1-Ly-51+PLET1+MHC class IIhi, which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1+Ly-51+ TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.

AB - Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam+UEA1-Ly-51+PLET1+MHC class IIhi, which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1+Ly-51+ TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.

KW - Animals

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Immunohistochemistry

KW - Immunophenotyping

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred CBA

KW - Phenotype

KW - Pregnancy Proteins/metabolism

KW - Real-Time Polymerase Chain Reaction

KW - Stem Cells/cytology

KW - Thymus Gland/cytology

KW - Transcriptome

U2 - 10.1016/j.celrep.2016.02.080

DO - 10.1016/j.celrep.2016.02.080

M3 - Journal article

C2 - 26997270

SN - 2639-1856

VL - 14

SP - 2819

EP - 2832

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -