2. Academic Validation
  3. Astrocyte-secreted cues promote neural maturation and augment activity in human forebrain organoids

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

  • Nat Commun. 2025 Mar 23;16(1):2845. doi: 10.1038/s41467-025-58295-3.
Honghui Zheng # 1,  Yilin Feng # 1,  Jiyuan Tang # 1,  Feifei Yu # 1,  Zitian Wang 1 2,  Jiani Xu 1,  Cheng Hai 1,  Mingyue Jiang 3 4,  Yifan Cheng 1,  Zhicheng Shao 5,  Ning Ma 6,  Peter E Lobie 1 2,  Shaohua Ma 7 8 9
Affiliations

Affiliations

  • 1 Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, China.
  • 2 Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, China.
  • 3 Guangzhou National Laboratory, Guangzhou, China.
  • 4 Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
  • 5 Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
  • 6 School of Basic Medical Sciences, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
  • 7 Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, China. ma.shaohua@sz.tsinghua.edu.cn.
  • 8 Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, China. ma.shaohua@sz.tsinghua.edu.cn.
  • 9 Key Lab of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Tsinghua Shenzhen International Graduate School, Shenzhen, China. ma.shaohua@sz.tsinghua.edu.cn.
  • # Contributed equally.
PMID: 40122897 DOI: 10.1038/s41467-025-58295-3
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.

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