scholarly journals Platelet-derived growth factor receptor-alpha positive cardiac progenitor cells derived from multipotent germline stem cells are capable of cardiomyogenesis in vitro and in vivo

Oncotarget ◽  
2017 ◽  
Vol 8 (18) ◽  
pp. 29643-29656 ◽  
Author(s):  
Bang-Jin Kim ◽  
Yong-Hee Kim ◽  
Yong-An Lee ◽  
Sang-Eun Jung ◽  
Yeong Ho Hong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Cardiac Progenitor Cells ◽  
Germline Stem Cells ◽  
Factor Receptor Alpha

Growth Factor Receptor-Bound Protein 10 (Grb10) Regulates Hematopoietic Stem Cell Renewal

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 248-248
Author(s):  
Xiao Yan ◽  
Heather A. Himburg ◽  
Phuong L. Doan ◽  
Mamle Quarmyne ◽  
Nelson J. Chao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Growth Factor Receptor ◽  
Self Renewal ◽  
Donor Cells ◽  
Growth Factor Receptor Bound

Abstract The mechanisms which regulate HSC regeneration following stress or injury remain poorly understood. Precise study of HSCs during regeneration has been impeded by the rarity of the HSC population and depletion of phenotypic HSCs early following genotoxic stresses, such as total body irradiation (TBI). We isolated bone marrow (BM) ckit+sca-1+lin- (KSL) cells, which are enriched for HSCs, from adult C57Bl6 mice before and at several time points following TBI, as a means to map the dynamic molecular response of HSC regeneration. Following 550cGy TBI, BM KSL cells were depleted by 7 days post-TBI, whereas KSL cell recovery was evident at day+14. We isolated BM KSL cells and myeloid progenitor cells (c-kit+sca-1-lin- cells) at day +14 and compared the gene expression profile of regenerating HSCs versus steady state HSCs (non-irradiated) and committed progenitor cells. We identified growth factor receptor-bound protein 10 (Grb10), a co-receptor which regulates Insulin Receptor/IGF-1 signaling, to be significantly overexpressed in regenerating BM KSL cells compared to non-irradiated KSL cells (3.3 fold, p<0.0001). Grb10 is a member of the family of imprinted genes which are predominately expressed in numerous stem cell populations, including embryonic stem cells, skin and muscle stem cells. Viral shRNA-mediated knockdown of Grb10 in BM KSL cells caused a significant decrease in KSL cells and colony forming cells (CFCs) in detected in 7 day culture (p=0.03 and p=0.002, respectively). Furthermore, mice which were competitively transplanted with Grb10-deficient KSL cells had 10-fold decreased donor, multilineage hematopoietic cell engraftment than mice transplanted with Grb10-expressing HSCs (p=0.007 for %CD45.1+ donor cells). Secondary competitive repopulation assays confirmed > 10-fold deficit in long-term repopulating capacity in Grb10 deficient KSL cells compared to Grb10 expressing KSL cells (p=0.006 for %CD45.1+ donor cells in secondary mice). In order to examine the effect of Grb10-deficiency on HSC fate and hematopoiesis in vivo, we generated maternally-derived Grb10-deficient mice. Heterozygous 8-week old Grb10m/+ (1 mutant allele, 1 wild type allele) were found to have 10-fold decreased Grb10 expression in BM lin- cells and had normal range complete blood counts. However, BM CFCs were significantly decreased in Grb10m/+ mice compared to Grb10+/+ mice (p=0.006) and competitive repopulation assays demonstrated significantly decreased donor hematopoietic cell repopulation in recipient mice transplanted with Grb10m/+ BM cells versus mice transplanted with Grb10+/+ BM cells (1/14, 7% vs. 5/14, 38% of mice with > 0.1% donor CD45.2+ cells). These results suggest that Grb10 regulates HSC self-renewal in vitro and in vivo. Mechanistically, Grb10m/+ mice displayed no alterations in the cell cycle status or frequency of apoptotic cells within BM HSCs compared to Grb10+/+ mice. However, single cytokine functional screening suggested that Grb10 regulates SCF-mediated proliferation of HSCs. Grb10m/+ BM KSL cells generated significantly less CFCs in culture in response to SCF treatment compared to Grb10+/+ KSL cells (p=0.008). Commensurate with this, SCF-mediated activation of mTOR was significantly increased in Grb10m/+ KSL cells compared to that observed in Grb10+/+ KSL cells (p=0.006). These data suggest that cytokine-mediated induction of mTOR signaling, which has been shown to deplete functional HSCs, is antagonized by Grb10, and that Grb10 is necessary to block cytokine-mediated HSC differentiation in vitro and in vivo. Grb10 represents a novel regulator of HSC fate determination and a new mechanistic target to facilitate HSC self-renewal. Studies are underway to determine whether Grb10 is also necessary for HSC regeneration after TBI. Disclosures No relevant conflicts of interest to declare.

scholarly journals Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo

Neoplasia ◽  
2009 ◽  
Vol 11 (8) ◽  
pp. 732-W7 ◽  
Author(s):  
Debora Faraone ◽  
Maria Simona Aguzzi ◽  
Gabriele Toietta ◽  
Angelo M. Facchiano ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Melanoma Growth

scholarly journals Platelet-Derived Growth Factor Receptor Alpha as a Marker of Mesenchymal Stem Cells in Development and Stem Cell Biology

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ramin M. Farahani ◽  
Munira Xaymardan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Growth Factor Receptor ◽  
Stem Cell Marker ◽  
Factor Receptor Alpha ◽  
Lines Of Evidence

Three decades on, the mesenchymal stem cells (MSCs) have been intensively researched on the bench top and used clinically. However, ambiguity still exists in regard to their anatomical locations, identities, functions, and extent of their differentiative abilities. One of the major impediments in the quest of the MSC research has been lack of appropriatein vivomarkers. In recent years, this obstacle has been resolved to some degree as PDGFRαemerges as an important mesenchymal stem cell marker. Accumulating lines of evidence are showing that the PDGFRα+cells reside in the perivascular locations of many adult interstitium and fulfil the classic concepts of MSCsin vitroandin vivo. PDGFRαhas long been recognised for its roles in the mesoderm formation and connective tissue development during the embryogenesis. Current review describes the lines of evidence regarding the role of PDGFRαin morphogenesis and differentiation and its implications for MSC biology.

scholarly journals Sustained Platelet-Derived Growth Factor Receptor α Signaling in Osteoblasts Results in Craniosynostosis by Overactivating the Phospholipase C-γ Pathway

2008 ◽  
Vol 29 (3) ◽  
pp. 881-891 ◽  
Author(s):  
Anne Moenning ◽  
Richard Jäger ◽  
Angela Egert ◽  
Wolfram Kress ◽  
Eva Wardelmann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Bone Matrix ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Platelet Derived Growth Factor ◽  
Cranial Sutures ◽  
First Time

ABSTRACT The development and growth of the skull is controlled by cranial sutures, which serve as growth centers for osteogenesis by providing a pool of osteoprogenitors. These osteoprogenitors undergo intramembranous ossification by direct differentiation into osteoblasts, which synthesize the components of the extracellular bone matrix. A dysregulation of osteoblast differentiation can lead to premature fusion of sutures, resulting in an abnormal skull shape, a disease called craniosynostosis. Although several genes could be linked to craniosynostosis, the mechanisms regulating cranial suture development remain largely elusive. We have established transgenic mice conditionally expressing an autoactivated platelet-derived growth factor receptor α (PDGFRα) in neural crest cells (NCCs) and their derivatives. In these mice, premature fusion of NCC-derived sutures occurred at early postnatal stages. In vivo and in vitro experiments demonstrated enhanced proliferation of osteoprogenitors and accelerated ossification of osteoblasts. Furthermore, in osteoblasts expressing the autoactivated receptor, we detected an upregulation of the phospholipase C-γ (PLC-γ) pathway. Treatment of differentiating osteoblasts with a PLC-γ-specific inhibitor prevented the mineralization of synthesized bone matrix. Thus, we show for the first time that PDGFRα signaling stimulates osteogenesis of NCC-derived osteoblasts by activating the PLC-γ pathway, suggesting an involvement of this pathway in the etiology of human craniosynostosis.

scholarly journals Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sunhye Shin ◽  
Yiyu Pang ◽  
Jooman Park ◽  
Lifeng Liu ◽  
Brandon E Lukas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Dynamic Control ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Receptor Alpha ◽  
Factor Receptor Alpha ◽  
Adipose Tissue Development ◽  
Lineage Tracking

Adipocytes arise from distinct progenitor populations during developmental and adult stages but little is known about how developmental progenitors differ from adult progenitors. Here, we investigate the role of platelet-derived growth factor receptor alpha (PDGFRα) in the divergent regulation of the two different adipose progenitor cells (APCs). Using in vivo adipose lineage tracking and deletion mouse models, we found that developmental PDGFRα+ cells are adipogenic and differentiated into mature adipocytes, and the deletion of Pdgfra in developmental adipose lineage disrupted white adipose tissue (WAT) formation. Interestingly, adult PDGFRα+ cells do not significantly contribute to adult adipogenesis, and deleting Pdgfra in adult adipose lineage did not affect WAT homeostasis. Mechanistically, embryonic APCs require PDGFRα for fate maintenance, and without PDGFRα, they underwent fate change from adipogenic to fibrotic lineage. Collectively, our findings indicate that PDGFRα+ cells and Pdgfra gene itself are differentially required for WAT development and adult WAT homeostasis.

scholarly journals Platelet-Derived Growth Factor Receptor-β Constitutive Activity Promotes Angiogenesis In Vivo and In Vitro

2007 ◽  
Vol 27 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
Peetra U. Magnusson ◽  
Camilla Looman ◽  
Aive Åhgren ◽  
Yan Wu ◽  
Lena Claesson-Welsh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Constitutive Activity
Sign in / Sign up

Export Citation Format

Share Document