Non-Neuronal Release of Gamma-Aminobutyric Acid by Embryonic Pluripotent Stem Cells

Teng, Lin; Tang, Ya‐Bin; Sun, Fan; An, Shi-Min; Zhang, Chun; Yang, Xinjie; Lv, Haoyu; Lu, Qiumin; Cui, Yong-Yao; Hu, Jiancong; Zhu, Liang; Chen, Hongzhuan

doi:10.1089/scd.2013.0243

Cited by 13 publications

(11 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both GABAR types synergistically trigger intracellular calcium increase and the interplay between the GABARs and downstream effectors differentially modulates ESC proliferation and differentiation through selective activation of second messenger signaling cascades. Moreover, ESCs are reported to possess GABAergic circuit machinery and establish a GABA niche via release of the transmitter (28) .…”

Section: Gpcrs In Stem Cell Maintenancementioning

confidence: 99%

G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells

et al. 2015

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) are a large class of transmembrane receptors categorized into five distinct families: rhodopsin, secretin, adhesion, glutamate, and frizzled. They bind and regulate 80% of all hormones and account for 20-50% of the pharmaceuticals currently on the market. Hundreds of GPCRs integrate and coordinate the functions of individual cells, mediating signaling between various organs. GPCRs are crucial players in tumor progression, adipogenesis, and inflammation. Several studies have also confirmed their central roles in embryonic development and stem cell maintenance. Recently, GPCRs have emerged as key players in the regulation of cell survival, proliferation, migration, and self-renewal in pluripotent (PSCs) and cancer stem cells (CSCs). Our study and other reports have revealed that the expression of many GPCRs is modulated during the generation of induced PSCs (iPSCs) or CSCs as well as during CSC sphere formation. These GPCRs may have crucial roles in the regulation of selfrenewal and other biological properties of iPSCs and CSCs. This review addresses the current understanding of the role of GPCRs in stem cell maintenance and somatic reprogramming to PSCs or CSCs. [BMB Reports 2015; 48(2): 68-80]

show abstract

Section: Gpcrs In Stem Cell Maintenancementioning

confidence: 99%

G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…This kind of negative regulatory feedback loop has been proven to control stem cell pool size and cancer growth. Autocrine γ-Aminobutyric acid (GABA), a classic neurotransmitter, lead to the S phase arrest of the cell cycle in ES cells [28, 29]. …”

Section: Discussionmentioning

confidence: 99%

“…The cell culture and the pluripotency monitoring were performed as indicated in the previous description [29, 50, 51]. ECS cells were expanded in DMEM (Life Technology, Catalog Number 11995, glutamate free) supplemented with 10% fetal bovine serum (FBS) and 1% GlutaMAX (glutamine).…”

Section: Methodsmentioning

confidence: 99%

Autocrine glutamatergic transmission for the regulation of embryonal carcinoma stem cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

Glutamate behaves as the principal excitatory neurotransmitter in the vertebrate central nervous system and recently demonstrates intercellular signaling activities in periphery cancer cells. How the glutamatergic transmission is organized and operated in cancer stem cells remains undefined. We have identified a glutamatergic transmission circuit in embryonal carcinoma stem cells. The circuit is organized and operated in an autocrine mechanism and suppresses the cell proliferation and motility. Biological analyses determined a repertoire of glutamatergic transmission components, glutaminase, vesicular glutamate transporter, glutamate NMDA receptor, and cell membrane excitatory amino-acid transporter, for glutamate biosynthesis, package for secretion, reaction, and reuptake in mouse and human embryonal carcinoma stem cells. The glutamatergic components were also identified in mouse transplanted teratocarcinoma and in human primary teratocarcinoma tissues. Released glutamate acting as the signal was directly quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Genetic and pharmacological abolishment of the endogenously released glutamate-induced tonic activation of the NMDA receptors increased the cell proliferation and motility. The finding suggests that embryonal carcinoma stem cells can be actively regulated by establishing a glutamatergic autocrine/paracrine niche via releasing and responding to the transmitter.

show abstract

“…The mouse P19 ECS cell line was obtained from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). The culture and monitoring of pluripotency of the embryonic pluripotent cells were performed as described in our previous report 51 52 . ES cells were grown with irradiated mouse embryonic fibroblasts (MEFs) as feeder layer in KO-DMEM supplemented with 1/10000 (v/v) LIF, 1/500 (v/v) β-mercaptoethanol, 1/100 (v/v) L-glutamine, 1/100 (v/v) non-essential amino acids, and 15% FBS.…”

Section: Methodsmentioning

confidence: 99%

Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling

Sun

Ding

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

Embryonic pluripotent cells are sensitive to genotoxicity though they need more stringent genome integrity to avoid compromising multiple cell lineages and subsequent generations. However it remains unknown whether the cells are susceptible to adrenergic stress which can induce somatic cell genome lesion. We have revealed that adrenergic stress mediators cause DNA damage of the cells through the β2 adrenergic receptor/adenylate cyclase/cAMP/PKA signalling pathway involving an induction of intracellular reactive oxygen species (ROS) accumulation. The adrenergic stress agonists adrenaline, noradrenaline, and isoprenaline caused DNA damage and apoptosis of embryonic stem (ES) cells and embryonal carcinoma stem cells. The effects were mimicked by β2 receptor-coupled signalling molecules and abrogated by selective blockade of β2 receptors and inhibition of the receptor signalling pathway. RNA interference targeting β2 receptors of ES cells conferred the cells the ability to resist the DNA damage and apoptosis. In addition, adrenergic stimulation caused a consistent accumulation of ROS in the cells and the effect was abrogated by β2 receptor blockade; quenching of ROS reversed the induced DNA damage. This finding will improve the understanding of the stem cell regulatory physiology/pathophysiology in an adrenergic receptor subtype signalling mechanism.

show abstract

Non-Neuronal Release of Gamma-Aminobutyric Acid by Embryonic Pluripotent Stem Cells

Cited by 13 publications

References 40 publications

G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells

G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells

Autocrine glutamatergic transmission for the regulation of embryonal carcinoma stem cells

Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling

Contact Info

Product

Resources

About