Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors
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Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors. / Łyszkiewicz, Marcin; Ziętara, Natalia; Föhse, Lisa; Puchałka, Jacek; Diestelhorst, Jana; Witzlau, Katrin; Prinz, Immo; Schambach, Axel; Krueger, Andreas.
in: BLOOD, Jahrgang 125, Nr. 3, 15.01.2015, S. 457-64.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -