Role of alpha‐ and beta‐adrenergic receptors in cardiomyocyte differentiation from murine‐induced pluripotent stem cells

Li, Xiaoli; Zeng, Dongqiang; Chen, Yan; Ding, Lei; Li, Wen-Ju; Wei, Ting; Ou, Dong-Bo; Song, Yan; Wang, Bin; Zheng, Qiangsun

doi:10.1111/cpr.12310

Cited by 6 publications

(4 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a research goal, ERF knockdown to confirm T-cell CTL reactivity under SMAD related to TGFβ pathway, two-step cloned TIL was cultured for these research. That is, normal TIL culture in the first step, and TIL was cultured in the functional induction and inhibition at the second step as in the previous report [14,46] . Discussion:…”

Section: Experimental Results On the New Modulementioning

confidence: 99%

“…Tumor-infiltrating lymphocytes (TILs, a group of heterogeneous T-cells) have made use of both (1) administrating TIL adoptive cell therapy (ACT) [1] and (2) studying immune characteristics regarding T-cell, B-cell, and NK cells, macrophage and neutrophil within the tumor tissues [2] so that TIL have been engaged to effectively treat different tumors and discover characteristics of immune response to tumor cells from the patients with tumor diseases to guide other immune therapy under the TIL characteristics from patients [3-4 . In the early periods between 1989 and 1994, we discovered that TIL could be used to treat solid tumors under more than three hundred TIL treatments for patients with solid tumors, but TIL ACT was found to have variable efficacy in treating solid tumor diseases during the early periods [5][6][7][8][9][10] . In order to study the efficacy of treating solid tumor diseases, we began to set up tumor tissue inventory [11] and study TIL genomic profiles, including setting up single-cell genomics profiles from TILs (including single-cell mRNA differential display from TIL published in 2007 [12] and single-cell RNA-seq from TIL published in 2013 [13] ), establishing TIL quantitative network published in 2015 [14] , and studying machine-learning analysis by artificial intelligence (AI) from TIL in 2022 [15] . Now, we know at least three quantitative networks, including the TCR signaling pathway, IL2 pathway, and TGF-β pathway, for guidance in immune diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spatial-timely Quantitative Network Analysis for TGF-β pathway of Tumor Infiltrating Lymphocytes

Yang,

Li,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Tumor-infiltrating lymphocytes (TILs) are to be subject to clinical applications by cultured TIL infusion in vivo for adoptive cell therapy (ACT) and by ex vivo TIL analysis for determining immune characteristics to kill autologous tumor cells so that TIL has been administrated tumor’s patients to immune-cell therapy and analyze patients’ immune characteristics for tumor diseases. To study the TIL features, we have established quantitative network modeling by TIL’s TCR signaling pathway, IL2 pathway, and TGF-β pathway for personalized immunotherapy for more than fifteen years. However, machine-learning analysis still has some challenges under the traditional quantitative pathway for network configurations to apply for patient treatment. For example, multiple protein complexes competing for downstream DNA binding-site or protein-protein complex will generate different effects. To address this question, we report here a temporal-spatial quantification network, termed a spatial-timely quantification network, to address the spatial-timely competition of complex proteins binding to downstream proteins or DNA in network analysis. After studying spatial-timely quantitative network modeling by TGF-β pathway activity in spatial-timely order, we discover that multiple protein complexes using spatial-timely quantitative networks are much better than traditional quantitative networks. Once the new system modeling is established, we can further analyze all pathways, such as the TCR signaling pathway and IL2 pathway from TIL, for different immunotherapy.

show abstract

Section: Experimental Results On the New Modulementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spatial-timely Quantitative Network Analysis for TGF-β pathway of Tumor Infiltrating Lymphocytes

Yang,

Li,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…By investigating the osteogenic mechanism of MScs, certain scholars have reported that β-AR activators inhibit osteogenesis of MScs, while blockers promote osteogenesis of MScs (54,55). The β-AR activator also inhibits the signaling pathway associated with osteogenesis by regulating expression of MEK and ERK1/2 phosphorylation, thereby inhibiting differentiation of BMScs into osteoblast-like cells in vitro (56,57). The osteogenic capacity of MScs has been established (58).…”

Section: Discussionmentioning

confidence: 99%

Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration

et al. 2021

View full text Add to dashboard Cite

The present study aimed to investigate the effect of β-receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular regulatory mechanisms. An implant osseointegration model using the tibial metaphysis of New Zealand rabbits was established. The rabbits were divided into control and low-, medium-and high-dose propranolol groups. The formation of implant osseointegration was detected by X-ray scanning. Mesenchymal stem cells (MScs) and osteoblasts (OBs) were isolated and cultured in vitro, isoproterenol was supplemented to simulate sympathetic action and propranolol was subsequently administrated. The effect of propranolol on cell proliferation and osteogenic differentiation were assessed by EdU, flow cytometry, alizarin red staining and alkaline phosphatase (ALP) detection. The expression levels of bone morphogenetic protein (BMP)2, RUNX family transcription factor (RunX)2, collagen (cOL)-1, osteocalcin (OcN) and β2-adrenergic receptor (AR) were detected by immunofluorescence, reverse transcription-quantitative PcR and western blot assay. Propranolol effectively promoted implant osseointegration in vivo, facilitated proliferation of OBs, inhibited proliferation of MScs and enhanced osteogenic differentiation of OBs and MScs. The calcium content and ALP activity of cells treated with propranolol were markedly higher than in the control group. Propranolol also elevated mRNA and protein expression levels of BMP2, RunX2, cOL-1 and OcN in tissue and cells, and decreased the expression of β2-AR. The present study demonstrated that the β-receptor blocker propranolol promoted osteogenic differentiation of OBs and MScs and enhanced implant osseointegration. The present study provided a novel insight into the application and regulatory mechanisms of propranolol.

show abstract

“…CM-like induction requires the inhibition of Wnt signaling via Wnt inhibitors [156,[159][160][161], such as IWR1 and IWP2, as well as the addition of various growth factors (GFs), such as FGF (fibroblast GF) and VEGF (vascular endothelial GF) [157,159,161,163,165]. In addition, modulation of MAPK signaling, using SB203580 [133] and PD98059 [167] (both MAPK inhibitors), or Rho-kinase inhibitors (H1152) [158] are utilised. In contrast, differentiation towards SAN-like cells mandates inhibition of GF-, including Activin-and Nodal-signaling using inhibitors such as PD 173074 (FGF signaling inhibitor) and SB-431542 (Activin/Nodal/TGFβ signaling inhibitor) [159].…”

Section: Targeted Differentiationmentioning

confidence: 99%

(Re-)programming of subtype specific cardiomyocytes

Hausburg

Jung

Wolfien

et al. 2017

Advanced Drug Delivery Reviews

View full text Add to dashboard Cite

Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing.

show abstract

Role of alpha‐ and beta‐adrenergic receptors in cardiomyocyte differentiation from murine‐induced pluripotent stem cells

Abstract: These results demonstrate that activation of ARs, particularly of α -ARs, promoted miPSC differentiation into cardiac lineages via MEK-ERK1/2 signalling.

Cited by 6 publications

References 57 publications

Spatial-timely Quantitative Network Analysis for TGF-β pathway of Tumor Infiltrating Lymphocytes

Spatial-timely Quantitative Network Analysis for TGF-β pathway of Tumor Infiltrating Lymphocytes

Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration

(Re-)programming of subtype specific cardiomyocytes

Contact Info

Product

Resources

About