Human dorsal forebrain organoids show differentiation-state-specific protein secretion
Summary: The human brain microenvironment undergoes dynamic changes during development, which have been incompletely characterized in in vitro models including neural organoids. Here, we used liquid chromatography-mass spectrometry to investigate proteome and secretome changes in human dorsal forebr...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225011964 |
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| author | Zeynep Yentür Theresa Kagermeier Kseniia Sarieva Mohamed A. Jarboui Katharina Becker Simone Mayer |
| author_facet | Zeynep Yentür Theresa Kagermeier Kseniia Sarieva Mohamed A. Jarboui Katharina Becker Simone Mayer |
| author_sort | Zeynep Yentür |
| collection | DOAJ |
| description | Summary: The human brain microenvironment undergoes dynamic changes during development, which have been incompletely characterized in in vitro models including neural organoids. Here, we used liquid chromatography-mass spectrometry to investigate proteome and secretome changes in human dorsal forebrain organoids derived from three hiPSC lines at days 20, 35, and 50 of differentiation. Proteome and immunohistochemical analysis revealed reduced proliferation and increased differentiation of progenitor cells gradually over time. In contrast, secretome analysis showed distinct characteristics at each timepoint — notably, at day 35, the numbers of cell adhesion molecules, synaptic proteins, and proteases were increased. Taken together, we present a resource describing the dynamic features of a neural organoid proteome and secretome across different genetic backgrounds. We describe the unique niche composition of neural organoids during the period of neurogenesis and suggest that synaptic proteins may play a role in guiding neurogenesis. |
| format | Article |
| id | doaj-art-abb9349366a64d729645fc030aac2ca6 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-abb9349366a64d729645fc030aac2ca62025-08-20T02:44:28ZengElsevieriScience2589-00422025-07-0128711293510.1016/j.isci.2025.112935Human dorsal forebrain organoids show differentiation-state-specific protein secretionZeynep Yentür0Theresa Kagermeier1Kseniia Sarieva2Mohamed A. Jarboui3Katharina Becker4Simone Mayer5The Heidelberg Academy of Sciences and Humanities, Heidelberg, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; International Max Planck Research School, Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, GermanyHertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, GermanyHertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; International Max Planck Research School, Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, GermanyCore Facility for Medical Proteomics, Institute for Ophthalmic Research, University Clinic Tübingen, Tübingen, GermanyHertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyThe Heidelberg Academy of Sciences and Humanities, Heidelberg, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Zoological Institute, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany; Institute of Biological and Chemical Systems - Functional Molecular Systems, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany; Corresponding authorSummary: The human brain microenvironment undergoes dynamic changes during development, which have been incompletely characterized in in vitro models including neural organoids. Here, we used liquid chromatography-mass spectrometry to investigate proteome and secretome changes in human dorsal forebrain organoids derived from three hiPSC lines at days 20, 35, and 50 of differentiation. Proteome and immunohistochemical analysis revealed reduced proliferation and increased differentiation of progenitor cells gradually over time. In contrast, secretome analysis showed distinct characteristics at each timepoint — notably, at day 35, the numbers of cell adhesion molecules, synaptic proteins, and proteases were increased. Taken together, we present a resource describing the dynamic features of a neural organoid proteome and secretome across different genetic backgrounds. We describe the unique niche composition of neural organoids during the period of neurogenesis and suggest that synaptic proteins may play a role in guiding neurogenesis.http://www.sciencedirect.com/science/article/pii/S2589004225011964Natural sciencesBiological sciencesNeuroscienceTissue engineering |
| spellingShingle | Zeynep Yentür Theresa Kagermeier Kseniia Sarieva Mohamed A. Jarboui Katharina Becker Simone Mayer Human dorsal forebrain organoids show differentiation-state-specific protein secretion iScience Natural sciences Biological sciences Neuroscience Tissue engineering |
| title | Human dorsal forebrain organoids show differentiation-state-specific protein secretion |
| title_full | Human dorsal forebrain organoids show differentiation-state-specific protein secretion |
| title_fullStr | Human dorsal forebrain organoids show differentiation-state-specific protein secretion |
| title_full_unstemmed | Human dorsal forebrain organoids show differentiation-state-specific protein secretion |
| title_short | Human dorsal forebrain organoids show differentiation-state-specific protein secretion |
| title_sort | human dorsal forebrain organoids show differentiation state specific protein secretion |
| topic | Natural sciences Biological sciences Neuroscience Tissue engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225011964 |
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