Astrocyte-secreted cues promote neural maturation and augment activity in human forebrain organoids
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.
Authors
- Hai Cheng (ORCID: https://orcid.org/0000-0002-5305-9458)
- Honghui Zheng (ORCID: https://orcid.org/0009-0007-6734-7710)
- Peter E. Lobie (ORCID: https://orcid.org/0000-0002-8445-184X)
- Zi‐Tian Wang (ORCID: https://orcid.org/0000-0002-1245-3088)
- Ming Jiang (ORCID: https://orcid.org/0000-0003-0415-6021)
- Shaohua Ma (ORCID: https://orcid.org/0000-0002-4995-2032)
- Yilin Feng (ORCID: https://orcid.org/0000-0002-9423-2122)
- Ning Ma (ORCID: https://orcid.org/0000-0003-4982-4089)
- Yifan Cheng (ORCID: https://orcid.org/0000-0003-3957-9825)
- Zhicheng Shao (ORCID: https://orcid.org/0000-0003-4383-119X)
- Jiani Xu
- Jiyuan Tang (ORCID: https://orcid.org/0009-0000-9262-2533)
- Yu Feifei (ORCID: https://orcid.org/0009-0005-2305-6925)
Institutions
- Sun Yat-sen University (CN)
- University Town of Shenzhen (CN)
- Tsinghua–Berkeley Shenzhen Institute (CN)
- Children's Hospital of Fudan University (CN)
- State Key Laboratory of Medical Neurobiology
- Guangzhou Medical University (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-23
- DOI
- https://doi.org/10.1038/s41467-025-58295-3
- Citations
- 10
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 8.06
Funders
- National Natural Science Foundation of China-Yunnan Joint Fund