Astrocyte-secreted cues promote neural maturation and augment activity in human forebrain organoids

Honghui Zheng, Yilin Feng, Jiyuan Tang, Feifei Yu, Zitian Wang, Jiani Xu, Cheng Hai, Mingyue Jiang, Yifan Cheng, Zhicheng Shao, Ning Ma, Peter E. Lobie and Shaohua Ma ()
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Honghui Zheng: Tsinghua University
Yilin Feng: Tsinghua University
Jiyuan Tang: Tsinghua University
Feifei Yu: Tsinghua University
Zitian Wang: Tsinghua University
Jiani Xu: Tsinghua University
Cheng Hai: Tsinghua University
Mingyue Jiang: Guangzhou National Laboratory
Yifan Cheng: Tsinghua University
Zhicheng Shao: Fudan University
Ning Ma: Guangzhou Medical University
Peter E. Lobie: Tsinghua University
Shaohua Ma: Tsinghua University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Brain organoids have been proposed as suitable human brain model candidates for a variety of applications. However, the lack of appropriate maturation limits the transferability of such functional tools. Here, we present a method to facilitate neuronal maturation by integrating astrocyte-secreted factors into hPSC-derived 2D and 3D neural culture systems. We demonstrate that protein- and nutrient-enriched astrocyte-conditioned medium (ACM) accelerates neuronal differentiation with enlarged neuronal layer and the overproduction of deep-layer cortical neurons. We captured the elevated changes in the functional activity of neuronal networks within ACM-treated organoids using comprehensive electrophysiological recordings. Furthermore, astrocyte-secreted cues can induce lipid droplet accumulation in neural cultures, offering protective effects in neural differentiation to withstand cellular stress. Together, these data indicate the potential of astrocyte secretions to promote neural maturation.

Date: 2025
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DOI: 10.1038/s41467-025-58295-3

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