The clonal and molecular aetiology of emergency dendritic cell development

2020 ◽  
Author(s):  
Dawn S. Lin ◽  
Luyi Tian ◽  
Sara Tomei ◽  
Daniela Amann-Zalcenstein ◽  
Tracey M. Baldwin ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Immune Cell ◽  
Cell Development ◽  
Natural Immunity ◽  
Flt3 Ligand ◽  
Predominant Role ◽  
Transcriptional State ◽  
Cellular Barcoding

SummaryExtrinsic regulation of single haematopoietic stem and progenitor cell (HSPC) fate is crucial for immune cell development. Here, we examine the aetiology of Flt3 ligand (Flt3L)-mediated emergency development of type 1 conventional dendritic cells (cDC1s), which results in enhanced immunity against infections and cancer. Using cellular barcoding, we demonstrate a predominant role of enhanced clonal expansion and moderate contribution via recruitment of additional cDC1-generating HSPCs. The selective cDC1 expansion occurs primarily via multi-/oligo-potent clones, without compromising output to other lineages. To understand the molecular hallmarks early during a Flt3L response, we develop Divi-Seq to simultaneously profile cell division history, surface phenotype and transcriptional state of single HSPCs. We discover that Flt3L-responsive HSPCs maintain a proliferative ‘early progenitor’-like state, which leads to selective emergence of CD11c+cKit+ transitional precursors with high cellular output to cDC1s. These findings inform the mechanistic action of Flt3L in natural immunity and immunotherapy at a clonal level.

scholarly journals Structural Control on the Formation of Pb-Zn Deposits: An Example from the Pyrenean Axial Zone

Minerals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 489 ◽  
Author(s):  
Alexandre Cugerone ◽  
Emilien Oliot ◽  
Alain Chauvet ◽  
Jordi Gavaldà Bordes ◽  
Angèle Laurent ◽  
...  
Keyword(s):  
Structural Control ◽  
Predominant Role ◽  
Axial Zone ◽  
Regional Deformation ◽  
Structural Framework ◽  
Ore Bodies ◽  
Deformation Event ◽  
Key Parameter

Pb-Zn deposits and specifically Sedimentary-Exhalative (SEDEX) deposits are frequently found in deformed and/or metamorphosed geological terranes. Ore bodies structure is generally difficult to observe and its relationships to the regional structural framework is often lacking. In the Pyrenean Axial Zone (PAZ), the main Pb-Zn mineralizations are commonly considered as Ordovician SEDEX deposits in the literature. New structural field analyzes focusing on the relations between mineralization and regional structures allowed us to classify these Pb-Zn mineralizations into three types: (I) Type 1 corresponds to minor disseminated mineralization, probably syngenetic and from an exhalative source. (II) Type 2a is a stratabound mineralization, epigenetic and synchronous to the Variscan D1 regional deformation event and (III) Type 2b is a vein mineralization, epigenetic and synchronous to the late Variscan D2 regional deformation event. Structural control appears to be a key parameter in concentrating Pb-Zn in the PAZ, as mineralizations occur associated to fold hinges, cleavage, and/or faults. Here we show that the main exploited type 2a and type 2b Pb-Zn mineralizations are intimately controlled by Variscan tectonics. This study demonstrates the predominant role of structural study for unraveling the formation of Pb-Zn deposits especially in deformed/metamorphosed terranes.

scholarly journals The predominant role of IP3 type 1 receptors in activation of store-operated Ca2+ entry in liver cells

2011 ◽  
Vol 1808 (3) ◽  
pp. 745-751 ◽  
Author(s):  
L. Jones ◽  
L. Ma ◽  
J. Castro ◽  
T. Litjens ◽  
G.J. Barritt ◽  
...  
Keyword(s):  
Liver Cells ◽  
Predominant Role

scholarly journals Critical Role of the Matricellular Protein SPARC in Mediating Erythroid Progenitor Cell Development in Zebrafish

2012 ◽  
Vol 197 (3) ◽  
pp. 196-208 ◽  
Author(s):  
Rosa M. Ceinos ◽  
Eva Torres-Nuñez ◽  
Ruben Chamorro ◽  
Beatriz Novoa ◽  
Antonio Figueras ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Critical Role ◽  
Cell Development ◽  
Matricellular Protein ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cell

Immunoglobulin isotypes reveal a predominant role of type 1 immunity in multiple sclerosis

2001 ◽  
Vol 121 (1-2) ◽  
pp. 120-125 ◽  
Author(s):  
B Greve ◽  
C.G.M Magnusson ◽  
A Melms ◽  
R Weissert
Keyword(s):  
Multiple Sclerosis ◽  
Predominant Role ◽  
Immunoglobulin Isotypes

The role of the renin–angiotensin–aldosterone system in cardiovascular progenitor cell function

2009 ◽  
Vol 116 (4) ◽  
pp. 301-314 ◽  
Author(s):  
Cheng Qian ◽  
Regien G. Schoemaker ◽  
Wiek H. van Gilst ◽  
Anton J. M. Roks
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Function ◽  
Converting Enzyme ◽  
Endothelial Progenitor

Intervention in the RAAS (renin–angiotensin–aldosterone system) is one of the leading pharmacotherapeutic strategies, among others, used for the treatment of cardiovascular disease to improve the prognosis after myocardial infarction and to reduce hypertension. Recently, regenerative progenitor cell therapy has emerged as a possible alternative for pharmacotherapy in patients after myocardial infarction or ischaemic events elsewhere, e.g. in the limbs. Angiogenic cell therapy to restore the vascular bed in ischaemic tissues is currently being tested in a multitude of clinical studies. This has prompted researchers to investigate the effect of modulation of the RAAS on progenitor cells. Furthermore, the relationship between hypertension and endothelial progenitor cell function is being studied. Pharmacotherapy by means of angiotensin II type 1 receptor antagonists or angiotensin-converting enzyme inhibitors has varying effects on progenitor cell levels and function. These controversial effects may be explained by involvement of multiple mediators, e.g. angiotensin II and angiotensin-(1–7), that have differential effects on mesenchymal stem cells, haematopoietic progenitor cells and endothelial progenitor cells. Importantly, angiotensin II can either stimulate endothelial progenitor cells by improvement of vascular endothelial growth factor signalling, or invoke excessive production of reactive oxygen species causing premature senescence of these cells. On the other hand, angiotensin-(1–7) stimulates haematopoietic cells and possibly also endothelial progenitor cells. Furthermore, aldosterone, bradykinin and Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro) may also affect progenitor cell populations. Alternatively, the variability in effects of angiotensin II type 1 receptor and angiotensin-converting enzyme inhibition on cardiovascular progenitor cells might reflect differences between the various models or diseases with respect to circulating and local tissue RAAS activation. In the present review we discuss what is currently known with respect to the role of the RAAS in the regulation of cardiovascular progenitor cells.

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