Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors

TY - JOUR

T1 - Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors

AU - Łyszkiewicz, Marcin

AU - Ziętara, Natalia

AU - Föhse, Lisa

AU - Puchałka, Jacek

AU - Diestelhorst, Jana

AU - Witzlau, Katrin

AU - Prinz, Immo

AU - Schambach, Axel

AU - Krueger, Andreas

N1 - © 2015 by The American Society of Hematology.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - The origins of dendritic cells (DCs) and other myeloid cells in the thymus have remained controversial. In this study, we assessed developmental relationships between thymic dendritic cells and thymocytes, employing retrovirus-based cellular barcoding and reporter mice, as well as intrathymic transfers coupled with DC depletion. We demonstrated that a subset of early T-lineage progenitors expressed CX3CR1, a bona fide marker for DC progenitors. However, intrathymic transfers into nonmanipulated mice, as well as retroviral barcoding, indicated that thymic dendritic cells and thymocytes were largely of distinct developmental origin. In contrast, intrathymic transfers after in vivo depletion of DCs resulted in intrathymic development of non-T-lineage cells. In conclusion, our data support a model in which the adoption of T-lineage fate by noncommitted progenitors at steady state is enforced by signals from the thymic microenvironment unless niches promoting alternative lineage fates become available.

AB - The origins of dendritic cells (DCs) and other myeloid cells in the thymus have remained controversial. In this study, we assessed developmental relationships between thymic dendritic cells and thymocytes, employing retrovirus-based cellular barcoding and reporter mice, as well as intrathymic transfers coupled with DC depletion. We demonstrated that a subset of early T-lineage progenitors expressed CX3CR1, a bona fide marker for DC progenitors. However, intrathymic transfers into nonmanipulated mice, as well as retroviral barcoding, indicated that thymic dendritic cells and thymocytes were largely of distinct developmental origin. In contrast, intrathymic transfers after in vivo depletion of DCs resulted in intrathymic development of non-T-lineage cells. In conclusion, our data support a model in which the adoption of T-lineage fate by noncommitted progenitors at steady state is enforced by signals from the thymic microenvironment unless niches promoting alternative lineage fates become available.

KW - Animals

KW - Cell Differentiation

KW - Cell Lineage

KW - Cells, Cultured

KW - Dendritic Cells/cytology

KW - Flow Cytometry

KW - Mice

KW - Mice, Inbred C57BL

KW - Myeloid Cells/cytology

KW - Stem Cell Niche/immunology

KW - Stem Cells/cytology

KW - T-Lymphocytes/cytology

KW - Thymus Gland/cytology

U2 - 10.1182/blood-2014-07-592667

DO - 10.1182/blood-2014-07-592667

M3 - SCORING: Journal article

C2 - 25411428

VL - 125

SP - 457

EP - 464

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 3

ER -