scholarly journals ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta

2021 ◽  
Vol 22 (7) ◽  
pp. 3497
Author(s):  
Aiti Vizzini ◽  
Angela Bonura ◽  
Laura La Paglia ◽  
Antonino Fiannaca ◽  
Massimo La Rosa ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Fate ◽  
Transforming Growth Factor ◽  
Wide Spectrum ◽  
Transforming Growth Factor Β ◽  
Hematopoietic Stem ◽  
Hematopoietic Organ ◽  
Cerna Network ◽  
Species Specific ◽  
Post Transcriptional Regulation

The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to vertebrates, is an excellent model to investigate mechanisms of post-transcriptional regulation evolutionarily highly conserved in immune homeostasis. The combined use of NGS and bioinformatic analyses suggests that in the pharynx, the hematopoietic organ of Ciona robusta, the Tgf-β, Wnt, Hedgehog and FoxO pathways are involved in tissue homeostasis, as they are in human. Furthermore, ceRNA network interactions and 3′UTR elements analyses of Tgf-β, Wnt, Hedgehog and FoxO pathways genes suggest that different miRNAs conserved (cin-let-7d, cin-mir-92c, cin-mir-153), species-specific (cin-mir-4187, cin-mir-4011a, cin-mir-4056, cin-mir-4150, cin-mir-4189, cin-mir-4053, cin-mir-4016, cin-mir-4075), pseudogenes (ENSCING00000011392, ENSCING00000018651, ENSCING00000007698) and mRNA 3′UTR elements are involved in post-transcriptional regulation in an integrated way in C. robusta.

scholarly journals TGF-β signaling in the control of hematopoietic stem cells

Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3542-3550 ◽  
Author(s):  
Ulrika Blank ◽  
Stefan Karlsson
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Fate ◽  
Transforming Growth Factor ◽  
Wide Spectrum ◽  
Transforming Growth Factor Β ◽  
The Body ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Downstream Signaling

Abstract Blood is a tissue with high cellular turnover, and its production is a tightly orchestrated process that requires constant replenishment. All mature blood cells are generated from hematopoietic stem cells (HSCs), which are the self-renewing units that sustain lifelong hematopoiesis. HSC behavior, such as self-renewal and quiescence, is regulated by a wide array of factors, including external signaling cues present in the bone marrow. The transforming growth factor-β (TGF-β) family of cytokines constitutes a multifunctional signaling circuitry, which regulates pivotal functions related to cell fate and behavior in virtually all tissues of the body. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from homeostasis of the immune system to quiescence and self-renewal of HSCs. Here, we review key features and emerging concepts pertaining to TGF-β and downstream signaling pathways in normal HSC biology, featuring aspects of aging, hematologic disease, and how this circuitry may be exploited for clinical purposes in the future.

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control

2019 ◽  
Vol 97 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Laura P.M.H. de Rooij ◽  
Derek C.H. Chan ◽  
Ava Keyvani Chahi ◽  
Kristin J. Hope
Keyword(s):  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cell Fate ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Control Of Gene Expression ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Post Transcriptional Regulation

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Control of Hematopoietic Stem/Progenitor Cell Fate by Transforming Growth Factor-β

2003 ◽  
Vol 13 (6) ◽  
pp. 445-453 ◽  
Author(s):  
Nicolas Olivier Fortunel ◽  
Jacques Alexandre Hatzfeld ◽  
Marie-Noëlle Monier ◽  
Antoinette Hatzfeld
Keyword(s):  
Growth Factor ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Hematopoietic Stem

Lateral inhibition and cell fate during neurogenesis in Drosophila: the interactions between scute, Notch and Delta

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 733-742 ◽  
Author(s):  
C.V. Cabrera
Keyword(s):  
Transcriptional Regulation ◽  
Protein Expression ◽  
Cell Fate ◽  
Lateral Inhibition ◽  
Early Embryo ◽  
Causal Factors ◽  
Post Transcriptional Regulation

A comparison of the patterns of expression of AS-C (T3) RNA and protein suggests that an important level of regulation occurs post-transcriptionally. First, when the RNA is abundant in the early embryo the protein is barely detectable. Later, the protein starts to accumulate in only a subset of the nuclei of those cells expressing the RNA. Only the cells in the subsets become the neuroblasts. This post-transcriptional regulation is suppressed in embryos mutant for the genes Notch and Delta; where all cells expressing RNA accumulate protein. These findings suggest that deployment of T3 protein expression is one of the causal factors that assigns specific fates to the neuroblasts and, in consequence, a basis for the mechanism of lateral inhibition is proposed.

scholarly journals Serial transplantation reveals a critical role for endoglin in hematopoietic stem cell quiescence

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 688-696 ◽  
Author(s):  
Luciene Borges ◽  
Vanessa K. P. Oliveira ◽  
June Baik ◽  
Sean C. Bendall ◽  
Rita C. R. Perlingeiro
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Hematopoietic Stem ◽  
Conditional Deletion ◽  
Stem Cell Quiescence ◽  
Β Receptor ◽  
Serial Transplantation

Abstract Transforming growth factor β (TGF-β) is well known for its important function in hematopoietic stem cell (HSC) quiescence. However, the molecular mechanism underlining this function remains obscure. Endoglin (Eng), a type III receptor for the TGF-β superfamily, has been shown to selectively mark long-term HSCs; however, its necessity in adult HSCs is unknown due to embryonic lethality. Using conditional deletion of Eng combined with serial transplantation, we show that this TGF-β receptor is critical to maintain the HSC pool. Transplantation of Eng-deleted whole bone marrow or purified HSCs into lethally irradiated mice results in a profound engraftment defect in tertiary and quaternary recipients. Cell cycle analysis of primary grafts revealed decreased frequency of HSCs in G0, suggesting that lack of Eng impairs reentry of HSCs to quiescence. Using cytometry by time of flight (CyTOF) to evaluate the activity of signaling pathways in individual HSCs, we find that Eng is required within the Lin−Sca+Kit+–CD48− CD150+ fraction for canonical and noncanonical TGF-β signaling, as indicated by decreased phosphorylation of SMAD2/3 and the p38 MAPK-activated protein kinase 2, respectively. These findings support an essential role for Eng in positively modulating TGF-β signaling to ensure maintenance of HSC quiescence.

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