Developmental comparison between cerebral organoids in vitro and body’s cortices in vivo

WENJUAN -Fan; CHEN Xu-Dong; CHEN Yong-Fang; YANG Xu-Guang; JIN Shao-Ju; ZHAO Zhi-Jun; DENG Jin-Bo

doi:10.16098/j.issn.0529-1356.2023.04.002

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (4) : 383-391. DOI: 10.16098/j.issn.0529-1356.2023.04.002

Neurobiology

Developmental comparison between cerebral organoids in vitro and body’s cortices in vivo

FAN Wen-juan^1,2 CHEN Xu-dong¹ CHEN Yong-fang¹ YANG Xu-guang¹ JIN Shao-ju¹ZHAO Zhi-jun^1* DENG Jin-bo^1*

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Abstract

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5（E7.5）, E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body’s cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases’ models, but improvement of the existing technologies is necessary.

Key words

Cerebral organoid / Cerebral cortex / Induced pluripotent stem cell / Organoid culture / Immunofluorescence / Mouse

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FAN Wen-juan CHEN Xu-dong CHEN Yong-fang YANG Xu-guang JIN Shao-ju ZHAO Zhi-jun DENG Jin-bo. Developmental comparison between cerebral organoids in vitro and body’s cortices in vivo[J]. Acta Anatomica Sinica. 2023, 54(4): 383-391 https://doi.org/10.16098/j.issn.0529-1356.2023.04.002

References

［1］ Shi Y, Wu Q, Wang X. Modeling brain development and diseases with human cerebral organoids［J］. Curr Opin Neurobiol, 2021, 66: 103-115.

［2］Lancaster MA, Renner M, Martin CA, et al. Cerebral organoids model human brain development and microcephaly［J］. Nature, 2013, 501(7467): 373-379.

［3］Velasco S, Kedaigle AJ, Simmons SK, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex［J］. Nature, 2019, 570(7762): 523-527.

［4］Li Y, Muffat J, Omer A, et al. Induction of Expansion and Folding in Human Cerebral Organoids［J］. Cell Stem Cell, 2017, 20(3): 385-396.

［5］Fan WJ，Wang Q，Sun YZh, et al. Mouse induced pluripotent stem cell-derived cortical organoids and its biological characteristics［J］. Acta Anatomica Sinica,2017,48(4):387-396. (in Chinese)

范文娟,王倩,孙仪征,等.起源于小鼠诱导性多能干细胞的大脑皮质类器官的建立及其生物学特性［J］.解剖学报,2017,48(4):387-396.

［6］Xiong Y, Chen PH, Zhou Y. Neurobiology ［M］. 2nd ed. Beijing: Science Press, 2021:108-118. (in Chinese)

熊鹰，陈鹏慧，周艺. 神经生物学［M］. 第2版. 北京：科学出版社，2021:108-118.

［7］Takamori Y, Mori T, Wakabayashi T, et al. Nestin-positive microglia in adult rat cerebral cortex［J］. Brain Res, 2009, 1270: 10-18.

［8］Chew L, Aonuevo A, Knock E. Generating cerebral organoids from human pluripotent stem cells［J］. Methods Mol Biol, 2022, 2389: 177-199.

［9］Lancaster MA, Corsini NS, Wolfinger S, et al. Guided self-organization and cortical plate formation in human brain organoids［J］. Nat Biotechnol, 2017, 35(7): 659-666.

［10］Sidney LE, Branch MJ, Hopkinson A, et al. Concise review: evidence for CD34 as a common marker for diverse progenitors［J］. Stem Cells, 2014, 32(6):1380-1389.

［11］Qian X, Su Y, Adam CD, et al. Sliced human cortical organoids for modeling distinct cortical layer formation［J］. Cell Stem Cell, 2020, 26(5): 766-781.

［12］Qian X, Nguyen HN, Song MM, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure［J］. Cell, 2016, 165(5): 1238-1254.

［13］Renner M, Lancaster MA, Bian S, et al. Self-organized developmental patterning and differentiation in cerebral organoids［J］. EMBO J, 2017, 36(10): 1316-1329.

［14］Fan W, Sun Y, Shi Z, et al. Mouse induced pluripotent stem cells-derived Alzheimer’s disease cerebral organoid culture and neural differentiation disorders［J］. Neurosci Lett, 2019, 711: 134433.

［15］Yakoub AM. Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain［J］. Neural Regen Res, 2019, 14(5): 757-761.

［16］Giandomenico SL, Mierau SB, Gibbons GM, et al. Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output［J］. Nat Neurosci, 2019, 22(4): 669-679.

［17］Rash BG, Grove EA. Area and layer patterning in the developing cerebral cortex［J］. Curr Opin Neurobiol, 2006, 16(1): 25-34.

［18］Ha S, Tripathi PP, Daza RA, et al. Reelin mediates hippocampal Cajal-Retzius cell positioning and infrapyramidal blade morphogenesis［J］. J Dev Biol, 2020, 8(3):20.

［19］Causeret F, Moreau MX, Pierani A, et al. The multiple facets of Cajal-Retzius neurons［J］. Development, 2021, 148(11):199409.

［20］Fan WJ, Cheng WJ, Niu YL, et al. Normal development of Cajal-Retzius cells in mouse hippocampus and their changes in APPswe transgenic mice［J］. Acta Anatomica Sinica, 2010, 41(2): 211-218. (in Chinese)

范文娟, 程维杰, 牛艳丽等. 海马Cajal-Retzius细胞的正常发育及在APPswe转基因小鼠中的改变［J］.解剖学报, 2010, 41(2): 211-218.

［21］Gabriel E, Albanna W, Pasquini G, et al. Human brain organoids assemble functionally integrated bilateral optic vesicles［J］. Cell Stem Cell, 2021, 28(10): 1740-1757.

［22］Cakir B, Xiang Y, Tanaka Y, et al. Engineering of human brain organoids with a functional vascular-like system［J］. Nat Methods, 2019,16(11):1169-1175.

［23］Ahn Y, An JH, Yang HJ, et al. Human blood vessel organoids penetrate human cerebral organoids and form a vessel-like system［J］. Cells, 2021,10(8):2036.