Functional analysis of platelet-derived growth factor receptor-β in neural stem/progenitor cells

Xu, Guihua; Shen, Jie; Ikoma, Yoko; Fukuchi, Mamoru; Chung, Dang Thanh; Zheng, Yi-Nan; Hamashima, Takeru; Fujimori, Toshihiko; Tsuda, Masashi; Funa, Keiko; Sasahara, Masakiyo

doi:10.1016/j.neuroscience.2013.02.021

Cited by 20 publications

(19 citation statements)

References 42 publications

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“…In fact, there is no single marker that is unique to all pericytes. Nevertheless, there are a number of markers, such as PDGFR‐β (38, 39), α‐SMA (40, 41), NG2 (42, 43), Desmin (41, 44, 45), and RGS5 (regulator of G protein signaling 5) (46, 47), that are commonly used to verify pericyte identity (Table 1). In addition, CD146—also known as MCAM or MUC18—was found to be expressed on the surface of vascular endothelial cells, smooth muscle cells, and pericytes (48).…”

Section: Discussionmentioning

confidence: 99%

A systematic review: differentiation of stem cells into functional pericytes

Xu¹,

Gong²,

Heng³

et al. 2017

FASEB j.

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Pericytes are an integral cellular component of vascular structures. Numerous studies have investigated various stem cell types as potential sources of pericytes for application in cell-based therapy. The diverse stem cell types and variable experimental protocols of these studies make it imperative to evaluate the relevant scientific literature on the basis of a unified standard. The purpose of this systematic review is to rigorously evaluate the relevant scientific literature for conclusive evidence that stem cells can differentiate into functional pericytes. An online literature search was conducted up to July 2016. Eligible papers were evaluated on 4 pertinent criteria: ) appropriate controls,) markers to confirm pericyte phenotype, ) techniques for assessing pericyte functionality, and) differentiation efficiency of the protocol. Our search yielded 20 eligible studies (from 2006 to 2016), 12 of which were published in the past 5 yr. Of these 20 articles, only 1 had positive control, and 5 papers evaluated differentiation efficiency. The most commonly used pericyte markers were neuron-glial antigen 2, platelet-derived growth factor receptor-β, and α-smooth muscle actin. Three articles were associated with adipose stem cells, 4 with mesenchymal stem cells, and 7 with pluripotent stem cells, whereas the remaining 6 articles were based on other miscellaneous stem cell types. Stem cells can serve as a potential source of pericytes, but there should be standardized guidelines in future studies for assessing pericyte differentiation.-Xu, J., Gong, T., Heng, B. C., Zhang, C. F. A systematic review: differentiation of stem cells into functional pericytes.

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Section: Discussionmentioning

confidence: 99%

A systematic review: differentiation of stem cells into functional pericytes

Xu¹,

Gong²,

Heng³

et al. 2017

FASEB j.

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“…These findings were compatible with our previous report that showed an age‐dependency of PDGFR‐β function in NSPCs. PDGFR‐β regulates the self‐renewal, cell proliferation, and survival rates of NSPCs derived from neonatal mice but did not affect these functions in the NSPCs from advanced age mouse . Infarct size is another factor that may influence neuroblasts survival and migration toward the lesion .…”

Section: Discussionmentioning

confidence: 99%

PDGFR-β Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke

et al. 2015

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The neuroprotective agents and induction of endogenous neurogenesis remain to be the urgent issues to be established for the care of cerebral stroke. Platelet-derived growth factor receptor beta (PDGFR-b) is mainly expressed in neural stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain; however, the role in pathological neurogenesis remains elusive. To this end, we examined the role of PDGFR-b in the migration and proliferation of NSPCs after stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into the mice with conditional Pdgfrb-gene inactivation, including N-PRb-KO mice where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular pericytes, and E-PRb-KO mice with tamoxifen-induced systemic Pdgfrb-gene inactivation. The migration of the DCX 1 neuroblasts from the subventricular zone toward the ischemic core was highly increased in N-PRb-KO, but not in E-PRb-KO as compared to Pdgfrb-gene preserving control mice. We showed that CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in the ischemic lesion of N-PRb-KO mice. Furthermore, integrin a3 intrinsically expressed in NSPCs that critically mediates extracellular matrix-dependent migration, was upregulated in N-PRb-KO after MCAO. NSPCs isolated from N-PRb-KO rapidly migrated on the surface coated with collagen type IV or fibronectin that are abundant in vascular niche and ischemic core. PDGFR-b was suggested to be critically involved in pathological neurogenesis through the regulation of lesion-derived chemoattractant as well as intrinsic signal of NSPCs, and we believe that a coordinated regulation of these molecular events may be able to improve neurogenesis in injured brain for further functional recovery. STEM CELLS 2016;34:685-698 SIGNIFICANCE STATEMENTNeuroepithelium-specific Pdgfrb gene inactivation showed more robust ischemia-induced neurogenesis than that with Pdgfrb in Flox controls and in tamoxifen-induced ubiquitous Pdgfrb gene inactivated mice. Our results suggest that a coordinated regulation of lesion-derived migration inducing cue, CXCL12, as well as increased integrin a3 expression as an intrinsic factor of NSPCs may be able to improve neurogenesis in injured brain to further functional recovery.

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“…The expression of PDGFRB in self-renewal and neuronal differentiation was indispensable for the neonatal neural stem/progenitors, but not in the P28 mice (Xu et al 2013). Furthermore, BDNF and noggin, in addition to FGF2, were shown to be involved in PDGFRB-mediated regulation of neonatal neural stem/progenitors.…”

Section: Pdgf and Adult-neural Stem/progenitor Cellsmentioning

confidence: 99%

The Roles of PDGF in Development and During Neurogenesis in the Normal and Diseased Nervous System

Funa

Sasahara

2013

J Neuroimmune Pharmacol

157

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The four platelet-derived growth factor (PDGF) ligands and PDGF receptors (PDGFRs), α and β (PDGFRA, PDGFRB), are essential proteins that are expressed during embryonic and mature nervous systems, i.e., in neural progenitors, neurons, astrocytes, oligodendrocytes, and vascular cells. PDGF exerts essential roles from the gastrulation period to adult neuronal maintenance by contributing to the regulation of development of preplacodal progenitors, placodal ectoderm, and neural crest cells to adult neural progenitors, in coordinating with other factors. In adulthood, PDGF plays critical roles for maintenance of many specific cell types in the nervous system together with vascular cells through controlling the blood brain barrier homeostasis. At injury or various stresses, PDGF modulates neuronal excitability through adjusting various ion channels, and affecting synaptic plasticity and function. Furthermore, PDGF stimulates survival signals, majorly PI3-K/Akt pathway but also other ways, rescuing cells from apoptosis. Studies imply an involvement of PDGF in dendrite spine morphology, being critical for memory in the developing brain. Recent studies suggest association of PDGF genes with neuropsychiatric disorders. In this review, we will describe the roles of PDGF in the nervous system, from the discovery to recent findings, in order to understand the broad spectrum of PDGF in the nervous system. Recent development of pharmacological and replacement therapies targeting the PDGF system is discussed.

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Functional analysis of platelet-derived growth factor receptor-β in neural stem/progenitor cells

Cited by 20 publications

References 42 publications

A systematic review: differentiation of stem cells into functional pericytes

A systematic review: differentiation of stem cells into functional pericytes

PDGFR-β Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke

The Roles of PDGF in Development and During Neurogenesis in the Normal and Diseased Nervous System

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