Human striatal organoids derived from pluripotent stem cells recapitulate striatal development and compartments

Xinyu Chen; Hexige Saiyin; Yang Liu; Yuqi Wang; Xuan Li; Rong Ji; Lixiang Ma

doi:10.1371/journal.pbio.3001868

Human striatal organoids derived from pluripotent stem cells recapitulate striatal development and compartments

PLoS Biol. 2022 Nov 17;20(11):e3001868. doi: 10.1371/journal.pbio.3001868. eCollection 2022 Nov.

Authors

Xinyu Chen¹, Hexige Saiyin², Yang Liu¹, Yuqi Wang², Xuan Li³, Rong Ji⁴, Lixiang Ma¹

Affiliations

¹ Department of Anatomy and Histology & Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
² State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.
³ The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, P.R. China.
⁴ Department of Neurology, Huadong Hospital, Fudan University, Shanghai, P.R. China.

Abstract

The striatum links neuronal circuits in the human brain, and its malfunction causes neuronal disorders such as Huntington's disease (HD). A human striatum model that recapitulates fetal striatal development is vital to decoding the pathogenesis of striatum-related neurological disorders and developing therapeutic strategies. Here, we developed a method to construct human striatal organoids (hStrOs) from human pluripotent stem cells (hPSCs), including hStrOs-derived assembloids. Our hStrOs partially replicated the fetal striatum and formed striosome and matrix-like compartments in vitro. Single-cell RNA sequencing revealed distinct striatal lineages in hStrOs, diverging from dorsal forebrain fate. Using hStrOs-derived assembloids, we replicated the striatal targeting projections from different brain parts. Furthermore, hStrOs can serve as hosts for striatal neuronal allografts to test allograft neuronal survival and functional integration. Our hStrOs are suitable for studying striatal development and related disorders, characterizing the neural circuitry between different brain regions, and testing therapeutic strategies.

Copyright: © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Corpus Striatum
Humans
Neostriatum
Organoids*
Pluripotent Stem Cells*
Prosencephalon

Grants and funding

This work was supported by the National Natural Science Foundation of China (82071269 to LM), the National Key Research and Development Program of China (2018YFA0108004 and 2021YFA1101302 to LM), and the Shanghai Municipal Planning Commission of Science and Research Fund (201840009 to LM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.