scholarly journals A wave of embryonic bipotent T/lymphoid tissue inducer progenitors regulates the maturation of medullary thymic epithelial cells

2019 ◽  
Author(s):  
Ramy Elsaid ◽  
Sylvain Meunier ◽  
Odile Burlen-Defranoux ◽  
Francisca Soares-da-Silva ◽  
Thibaut Perchet ◽  
...  

SUMMARYMultiple waves of hematopoietic progenitors with distinct lineage potentials are differentially regulated in time and space. We show that the first thymic seeding progenitors comprise a unique population of bipotent cells that generate lymphoid tissue inducer and invariant Vγ5+ T cells. Both populations are of embryonic origin and induce the maturation of medullary thymic epithelial cells. Indeed, temporal depletion of the first wave of thymocytes results in a five-fold reduction of mature medullary thymic epithelial cells, after birth. We further show that these progenitors are of hematopoietic stem cell, and not, of yolk sac origin, despite the temporal overlap between the onset of lymphopoiesis and the transient expression of lymphoid transcripts in yolk sac precursors, that does not impact their strict erythro-myeloid potential. Our work highlights the relevance of the developmental timing on the emergence of different lymphoid subsets required for the establishment of a functionally diverse immune system.

Blood ◽  
2020 ◽  
Author(s):  
Ramy Elsaid ◽  
Sylvain Meunier ◽  
Odile Burlen-Defranoux ◽  
Francisca Soares-da-Silva ◽  
Thibaut Perchet ◽  
...  

During embryonic development, multiple waves of hematopoietic progenitors with distinct lineage potential are differentially regulated in time and space. Two different waves of thymic progenitors colonize the fetal thymus where they contribute to thymic organogenesis and homeostasis. The origin, the lineage differentiation potential of the first wave and their relative contribution in shaping the thymus architecture, remained, however, unclear. Here we show that the first wave of thymic progenitors comprises a unique population of bipotent cells generating lymphoid tissue inducer, in addition to invariant Vg5+ T cells. Transcriptional analysis revealed that innate lymphoid gene signatures and more precisely the lymphoid tissue inducer associated transcripts were expressed in the first but not in the second wave of thymic progenitors. Depletion of early thymic progenitors in a temporally-controlled manner showed that the progeny of the first wave is indispensable for the differentiation of autoimmune regulator expressing medullary thymic epithelial cells. We further show that these progenitors are of strict hematopoietic stem cell origin, despite the overlap between lymphopoiesis initiation and the transient expression of lymphoid associated transcripts in yolk sac erythro-myeloid restricted precursors. Our work highlights the relevance of the developmental timing on the emergence of different lymphoid subsets, required for the establishment of a functionally diverse immune system.


2013 ◽  
Vol 190 (10) ◽  
pp. 5110-5117 ◽  
Author(s):  
Enkhsaikhan Lkhagvasuren ◽  
Mie Sakata ◽  
Izumi Ohigashi ◽  
Yousuke Takahama

PLoS Genetics ◽  
2011 ◽  
Vol 7 (11) ◽  
pp. e1002348 ◽  
Author(s):  
Craig S. Nowell ◽  
Nicholas Bredenkamp ◽  
Stéphanie Tetélin ◽  
Xin Jin ◽  
Christin Tischner ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Beth Lucas ◽  
Andrea J. White ◽  
Emilie J. Cosway ◽  
Sonia M. Parnell ◽  
Kieran D. James ◽  
...  

2009 ◽  
Vol 88 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Živana Milićević ◽  
Novica M Milićević ◽  
Martti Laan ◽  
Pärt Peterson ◽  
Kai Kisand ◽  
...  

2006 ◽  
Vol 281 (50) ◽  
pp. 38617-38624 ◽  
Author(s):  
Baochun Zhang ◽  
Zhe Wang ◽  
Jane Ding ◽  
Pärt Peterson ◽  
William T. Gunning ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 626-634 ◽  
Author(s):  
Mathias M. Hauri-Hohl ◽  
Saulius Zuklys ◽  
Marcel P. Keller ◽  
Lukas T. Jeker ◽  
Thomas Barthlott ◽  
...  

Abstract The thymus constitutes the primary lymphoid organ responsible for the generation of naive T cells. Its stromal compartment is largely composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiologic process. The precise cellular and molecular mechanisms underlying thymic senescence are, however, only incompletely understood. Here, we demonstrate that TGF-β signaling in thymic epithelial cells exerts a direct influence on the cell's capacity to support thymopoiesis in the aged mouse as the physiologic process of thymic senescence is mitigated in mice deficient for the expression of TGF-βRII on thymic epithelial cells. Moreover, TGF-β signaling in these stromal cells transiently hinders the early phase of thymic reconstitution after myeloablative conditioning and hematopoietic stem cell transplantation. Hence, inhibition of TGF-β signaling decelerates the process of age-related thymic involution and may hasten the reconstitution of regular thymopoiesis after hematopoietic stem cell transplantation.


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