ArticleStem cells (Dayton, Ohio)2020
Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation.
Article in Stem cells (Dayton, Ohio), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Brain Organoids: Emerging Platforms for Modern Neuroscience.Brain sciences · 2026Review
- FTO-mediated mActa pharmaceutica Sinica. B · 2026Article
- Functional and evolutionary characteristics of human genes encoding cell surface receptors involved in the regulation of appetite.Journal of integrative bioinformatics · 2025Article
- The role of RGS12 in tissue repair and human diseases.Genes & diseases · 2025Review
- DRD4 Interacts with TGF-β Receptors to Drive Colorectal Cancer Metastasis Independently of Dopamine Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NewmedRxiv : the preprint server for health sciences · 2024Article
- A multicolor suite for deciphering population coding of calcium and cAMP in vivo.Nature methods · 2024Article
- In-silico and in-vitro morphometric analysis of intestinal organoids.PLoS computational biology · 2023Article
- Advances in the allostery of angiotensin II type 1 receptor.Cell & bioscience · 2023Review
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaMolecular neurobiology · 2023Article
- Engineering cerebral folding in brain organoids.Neural regeneration research · 2022Article
- Present Application and Perspectives of Organoid Imaging Technology.Bioengineering (Basel, Switzerland) · 2022Review
- Dopamine signaling impairs ROS modulation by mitochondrial hexokinase in human neural progenitor cells.Bioscience reports · 2021Article
- Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma.Cancer cell international · 2021Article
- Applications of brain organoids in neurodevelopment and neurological diseases.Journal of biomedical science · 2021Review
- Recent Trends and Perspectives in Cerebral Organoids Imaging and Analysis.Frontiers in neuroscience · 2021Review
- Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation.Stem cells (Dayton, Ohio) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intricate balance of neural stem cell (NSC) amplification and neurogenesis is central to nervous system development. Dopamine D1 receptor (DRD1) is a typical G protein-coupled receptor (GPCR) mainly expressed in neurogenic area, with high constitutive activity. The receptor appears in the embryonic period before the formation of mature synaptic contacts, which indicates that dopamine receptor and its constitutive activity play crucial roles in the embryonic brain development. Here, we found that DRD1 was enriched in human NSCs. Inhibition of the receptor activity by its inverse agonists promoted human NSCs proliferation and impeded its differentiation. These results were also mimicked by genetic knockdown of DRD1, which also blocked the effects of inverse agonists, suggesting a receptor-dependent manner. More interestingly, knock-in A229T mutant with reduced DRD1 constitutive activity by CRISPR-Cas9 genome editing technology resulted into increased endogenous human NSCs proliferation. These results were well reproduced in human cerebral organoids, and inhibition of the DRD1 constitutive activity by its inverse agonists induced the expansion and folding of human cerebral organoids. The anatomic analysis uncovered that decreasing the constitutive activity of DRD1 by its inverse agonists promoted the NSCs proliferation and maintenance that led to hindered cortical neurogenesis. Further mechanistic studies revealed that the PKC-CBP pathway was involved in the regulation by DRD1. Thus, our findings indicate that the constitutive activity of DRD1 and possibly other GPCRs plays an important role in the development of human nervous system.
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