scholarly journals Transforming Growth Factor β Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells

2016 ◽  
Vol 38 (4) ◽  
pp. 358-370 ◽  
Author(s):  
Rui Monteiro ◽  
Philip Pinheiro ◽  
Nicola Joseph ◽  
Tessa Peterkin ◽  
Jana Koth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Hemogenic Endothelium ◽  
Hematopoietic Stem

scholarly journals Smad4 is critical for self-renewal of hematopoietic stem cells

2007 ◽  
Vol 204 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Göran Karlsson ◽  
Ulrika Blank ◽  
Jennifer L. Moody ◽  
Mats Ehinger ◽  
Sofie Singbrant ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
In Vitro Proliferation ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Early Embryonic Lethality

Members of the transforming growth factor β (TGF-β) superfamily of growth factors have been shown to regulate the in vitro proliferation and maintenance of hematopoietic stem cells (HSCs). Working at a common level of convergence for all TGF-β superfamily signals, Smad4 is key in orchestrating these effects. The role of Smad4 in HSC function has remained elusive because of the early embryonic lethality of the conventional knockout. We clarify its role by using an inducible model of Smad4 deletion coupled with transplantation experiments. Remarkably, systemic induction of Smad4 deletion through activation of MxCre was incompatible with survival 4 wk after induction because of anemia and histopathological changes in the colonic mucosa. Isolation of Smad4 deletion to the hematopoietic system via several transplantation approaches demonstrated a role for Smad4 in the maintenance of HSC self-renewal and reconstituting capacity, leaving homing potential, viability, and differentiation intact. Furthermore, the observed down-regulation of notch1 and c-myc in Smad4−/− primitive cells places Smad4 within a network of genes involved in the regulation HSC renewal.

scholarly journals Role of Lipid Rafts in Hematopoietic Stem Cells Homing, Mobilization, Hibernation, and Differentiation

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 630 ◽  
Author(s):  
Munther Alomari ◽  
Dana Almohazey ◽  
Sarah Ameen Almofty ◽  
Firdos Alam Khan ◽  
Mohammad Al hamad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Lymphoid Cells ◽  
Membrane Microdomains ◽  
Hematopoietic Stem

Hematopoietic stem cells (HSCs) are multipotent, self-renewing cells that can differentiate into myeloid or lymphoid cells. The mobilization and differentiation processes are affected by the external environment, such as extracellular matrix and soluble molecules in the niche, where the lipid rafts (LRs) of the HSCs act as the receptors and control platforms for these effectors. LRs are membrane microdomains that are enriched in cholesterol, sphingolipid, and proteins. They are involved in diverse cellular processes including morphogenesis, cytokinesis, signaling, endocytic events, and response to the environment. They are also involved in different types of diseases, such as cancer, Alzheimer’s, and prion disease. LR clustering and disruption contribute directly to the differentiation, homing, hibernation, or mobilization of HSCs. Thus, characterization of LR integrity may provide a promising approach to controlling the fate of stem cells for clinical applications. In this review, we show the critical role of LR modification (clustering, disruption, protein incorporation, and signal responding) in deciding the fate of HSCs, under the effect of soluble cytokines such as stem cell factor (SCF), transforming growth factor- β (TGF-β), hematopoietic-specific phospholipase Cβ2 (PLC-β2), and granulocyte colony-stimulating factor (G-CSF).

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.

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