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Cell stem cell

Cell stem cell

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Generation of self-organized neuromusculoskeletal tri-tissue organoids from human pluripotent stem cells

Published:9 December 2024 DOI: 10.1016/j.stem.2024.11.005
Yao Yin, Wei Zhou, Jinkui Zhu, Ziling Chen, Linlin Jiang, Xuran Zhuang, Jia Chen, Jianfeng Wei, Xiaoxiang Lu, Yantong Liu, Wei Pang, Qinzhi Zhang, Yajing Cao, Zhuoya Li, Yuyan Zhu, Yangfei Xiang

Abstract

The human body function requires crosstalk between different tissues. An essential crosstalk is in the neuromusculoskeletal (NMS) axis involving neural, muscular, and skeletal tissues, which is challenging to model using human cells. Here, we describe the generation of three-dimensional, NMS tri-tissue organoids (hNMSOs) from human pluripotent stem cells through a co-development strategy. Staining, single-nucleus RNA sequencing, and spatial transcriptome profiling revealed the co-emergence and self-organization of neural, muscular, and skeletal lineages within individual organoids, and the neural domains of hNMSOs obtained a ventral-specific identity and produced motor neurons innervating skeletal muscles. The neural, muscular, and skeletal regions of hNMSOs exhibited maturation and established functional connections during development. Notably, structural, functional, and transcriptomic analyses revealed that skeletal support in hNMSOs benefited human muscular development. Modeling with hNMSOs also unveiled the neuromuscular alterations following pathological skeletal degeneration. Together, our study provides an accessible experimental model for future studies of human NMS crosstalk and abnormality.

Substances (9)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ascorbic Acid 50-81-7 C6H8O6 1626 suppliers $6.00-$2170.00
L-Glutamic acid 56-86-0 C5H9NO4 968 suppliers $5.00-$6413.62
Triton X-100 9002-93-1 (C2H4O)nC14H22O 532 suppliers $18.00-$610.00
Bovine albumin 9048-46-8 N/A 500 suppliers $15.00-$17060.00
INSULIN 11070-73-8 C254H377N65O75S6 191 suppliers $72.00-$2660.00
Y-27632 DIHYDROCHLORIDE 146986-50-7 C14H21N3O 170 suppliers $43.00-$2691.10
NBQX DISODIUM SALT 118876-58-7 C12H8N4O6S 115 suppliers $39.00-$1880.00
BRAIN DERIVED NEUROTROPHIC FACTOR, HUMAN 218441-99-7 C8H11NO4 64 suppliers $290.70-$1105.00
DAPI 47165-04-8 C16H15N5 13 suppliers $504.53-$504.53