scholarly journals Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development

Development ◽  
2020 ◽  
Vol 147 (12) ◽  
pp. dev178582 ◽  
Author(s):  
Dong Liu ◽  
Anastasia I. Kousa ◽  
Kathy E. O'Neill ◽  
Paul Rouse ◽  
Martyna Popis ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cell ◽  
Fetal Thymus ◽  
Cell State ◽  
Thymus Development

scholarly journals Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development

2019 ◽  
Author(s):  
Dong Liu ◽  
Anastasia I. Kousa ◽  
Kathy E. O’Neill ◽  
Francois Guillemot ◽  
Martyna Popis ◽  
...  
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
Direct Interaction ◽  
Thymic Epithelial Cells ◽  
Cell Repertoire ◽  
Thymic Tissue ◽  
Fetal Thymus ◽  
Thymus Development

AbstractThymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a direct interaction between NOTCH and FOXN1, the master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.

scholarly journals Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1945
Author(s):  
Sheyla González ◽  
Maximilian Halabi ◽  
David Ju ◽  
Matthew Tsai ◽  
Sophie X. Deng
Keyword(s):  
Notch Signaling ◽  
Progenitor Cell ◽  
Basal Layer ◽  
Notch Signaling Pathway ◽  
Basal Cells ◽  
Proliferation Markers ◽  
Limbal Epithelium ◽  
Asymmetric Divisions ◽  
Signaling Activation

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

scholarly journals Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer E. Cowan ◽  
Justin Malin ◽  
Yongge Zhao ◽  
Mina O. Seedhom ◽  
Christelle Harly ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
T Cell Development ◽  
Thymic Epithelial Cells ◽  
Fetal Life ◽  
Ribosomal Biogenesis ◽  
Transcriptional Program ◽  
Fetal Thymus ◽  
Thymus Development ◽  
And Function ◽  
Thymus Size

AbstractInteractions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.

Dietary N-carbamylglutamate and rumen-protected L-arginine supplementation during intrauterine growth restriction in undernourished ewes improve fetal thymus development and immune function

2018 ◽  
Vol 30 (11) ◽  
pp. 1522 ◽  
Author(s):  
Hao Zhang ◽  
Fangfang Zhao ◽  
Haitao Nie ◽  
Tiewei Ma ◽  
Ziyu Wang ◽  
...  
Keyword(s):  
Immune Function ◽  
Intrauterine Growth Restriction ◽  
National Research Council ◽  
Dietary Supplementation ◽  
Growth Restriction ◽  
Negative Effects ◽  
Fetal Thymus ◽  
Intrauterine Growth ◽  
Thymus Development ◽  
Hu Sheep

The aims of the present study were to determine whether dietary supplementation with N-carbamylglutamate (NCG) and rumen-protected l-arginine (RP-Arg) to underfed Hu sheep would improve fetal thymus development and immune function. From Day 35 to Day 110 of gestation, 32 Hu ewes carrying twin fetuses were randomly allocated to one of four groups (n = 8 per group): 100% National Research Council (NRC)-recommended nutrient requirements (CON), 50% NRC recommendations (RES), 50% NRC recommendations supplemented with 20 g day−1 RP-Arg (RES+ARG), and 50% NRC recommendations supplemented with 5 g day−1 NCG (RES+NCG). Medullary thickness was increased (P < 0.05) in RES compared with CON ewes, but was reduced (P < 0.05) in both RES+ARG and RES+NCG ewes compared with RES ewes. There were no differences in superoxide dismutase and glutathione peroxidase activity or malondialdehyde levels in the RES+ARG and RES+NCG groups compared with the CON group (P > 0.05). Concentrations of IgA, interleukin (IL)-1β and IL-10 in fetal umbilical cord blood were reduced (P < 0.05) in RES compared with CON ewes, but were increased (P < 0.05) in both RES+ARG and RES+NCG ewes. Expression of Bax, Fas and p53 mRNA was increased (P < 0.05) in RES compared with CON ewes, but were reduced (P > 0.05) in both RES+ARG and RES+NCG ewes. These results indicate that dietary supplementation with NCG and RP-Arg could help alleviate the negative effects of intrauterine growth restriction on fetal thymus development and immune function.

scholarly journals YY1 Expression Is Sufficient for the Maintenance of Cardiac Progenitor Cell State

Stem Cells ◽  
2017 ◽  
Vol 35 (8) ◽  
pp. 1913-1923 ◽  
Author(s):  
Serge Gregoire ◽  
Guang Li ◽  
Anthony C. Sturzu ◽  
Robert J. Schwartz ◽  
Sean M. Wu
Keyword(s):  
Progenitor Cell ◽  
Cardiac Progenitor Cell ◽  
Cell State

scholarly journals SOX2 maintains the quiescent progenitor cell state of postnatal retinal Muller glia

Development ◽  
2013 ◽  
Vol 140 (7) ◽  
pp. 1445-1456 ◽  
Author(s):  
N. Surzenko ◽  
T. Crowl ◽  
A. Bachleda ◽  
L. Langer ◽  
L. Pevny
Keyword(s):  
Progenitor Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Cell State
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