Evidence map›Paper›PMID 40867008›Full record

ArticleStem cell research & therapy2025

Directed and efficient generation of calretinin interneurons from human pluripotent stem cells.

Xuewei Du, Renli Qi, Congge Li, Wenpei Zhou, Shijiao Wang, Shenxing Wei, Runzhong Wu, Yu Yin, Tianqing Li, Xiaoqing Zhu

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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10 authors.

Xuewei Du *State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Renli Qi *Second Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
Congge LiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Wenpei ZhouState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Shijiao WangState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Shenxing WeiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Runzhong WuState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Yu YinState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
Tianqing LiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. litq@lpbr.cn.
Xiaoqing ZhuState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. zhuxq@lpbr.cn.ORCID http://orcid.org/0000-0001-7879-5956

Funding

Key Technologies Research and Development Program 2022YFA1103103National Natural Science Foundation of China 32271025Yunnan Provincial Department of Education Science Research Fund Project 2023Y0636Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Program on Basic Research 202401AY070001-236
6 · The paper itself

Abstract

backgroundSchizophrenia, autism, and epilepsy are associated with dysfunctions in cortical GABAergic interneurons. Calretinin-expressing interneurons, the most prominent type, constitute approximately 50% of human cortical GABAergic neurons and are closely linked to cognition. However, the difficulty in obtaining sufficient calretinin interneurons has significantly hindered the study of their development and functions. This study focuses on building an efficient protocol for generating calretinin interneurons, which is key to the brain development and regenerative medicine.

methodsNeuroepithelial stem cells (NESCs) were firstly generated from human pluripotent stem cells (hPSCs) using a previously established protocol, and subsequently treated with sonic hedgehog (SHH), purmorphamine and IWP2 to induce differentiation into calretinin interneurons. Single-cell RNA sequencing (scRNA-seq) was employed to analyze the transcriptional profiles of these interneurons, while their functional properties were assessed via transplantation.

resultsWe developed a robust protocol enabling the generation of approximately 80% calretinin interneurons from human pluripotent stem cells (hPSCs). NESCs were induced from hPSCs and differentiated into calretinin interneurons through modulation of Shh and Wnt signaling. These interneurons exhibited robust GABAergic action potentials. Upon transplantation, they successfully integrated into the mouse brain and matured into calretinin interneurons.

conclusionOur study presents an efficient protocol for generating calretinin interneurons from hPSCs, offering a valuable tool for investigating the development of calretinin interneurons. This approach holds potential for applications in regenerative medicine, disease modeling, and drug screening.

Indexed as

Calbindin 2Cell Culture TechniquesGABAergic NeuronsInterneuronsNeuroepithelial CellsNeurogenesisPluripotent Stem CellsAction PotentialsAnimalsBenzothiazolesHedgehog ProteinsHumansMiceMice, Inbred BALB CMorpholinesPurinesBenzothiazolesCalbindin 2Hedgehog ProteinsIWP-2 compoundMorpholinesPurinespurmorphamineCalretininCell differentiationInterneuronsNESCSingle cell

Identifiers

PMID40867008
PMCPMC12392484

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.