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Cite this page: Hill, M.A. (2021, September 25) Embryology Organoids. Retrieved from


Qian X, Su Y, Adam CD, Deutschmann AU, Pather SR, Goldberg EM, Su K, Li S, Lu L, Jacob F, Nguyen PTT, Huh S, Hoke A, Swinford-Jackson SE, Wen Z, Gu X, Pierce RC, Wu H, Briand LA, Chen HI, Wolf JA, Song H & Ming GL. (2020). Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation. Cell Stem Cell , , . PMID: 32142682 DOI.

Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation

Abstract Human brain organoids provide unique platforms for modeling development and diseases by recapitulating the architecture of the embryonic brain. However, current organoid methods are limited by interior hypoxia and cell death due to insufficient surface diffusion, preventing generation of architecture resembling late developmental stages. Here, we report the sliced neocortical organoid (SNO) system, which bypasses the diffusion limit to prevent cell death over long-term cultures. This method leads to sustained neurogenesis and formation of an expanded cortical plate that establishes distinct upper and deep cortical layers for neurons and astrocytes, resembling the third trimester embryonic human neocortex. Using the SNO system, we further identify a critical role of WNT/β-catenin signaling in regulating human cortical neuron subtype fate specification, which is disrupted by a psychiatric-disorder-associated genetic mutation in patient induced pluripotent stem cell (iPSC)-derived SNOs. These results demonstrate the utility of SNOs for investigating previously inaccessible human-specific, late-stage cortical development and disease-relevant mechanisms. Copyright © 2020 Elsevier Inc. All rights reserved. KEYWORDS: Brain organoid; DISC1; WNT; cerebral cortex; forebrain organoid; human iPSC; lamination; neurodevelopment; neuron fate specification; schizophrenia PMID: 32142682 DOI: 10.1016/j.stem.2020.02.002

Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids

Ai Tian, Julien Muffat and Yun Li Journal of Neuroscience 5 February 2020, 40 (6) 1186-1193; DOI:

In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. Brain organoids can be generated to model the cellular and structural development of the human brain, and allow the investigation of the intricate interactions between resident neural and glial cell types. Combined with new advances in gene editing, imaging, and genomic analysis, brain organoid technology can be applied to address questions pertinent to human brain development, disease, and evolution. However, the current iterations of brain organoids also have limitations in faithfully recapitulating the in vivo processes. In this perspective, we evaluate the recent progress in brain organoid technology, and discuss the experimental considerations for its utilization.



Science. 2019 Jun 7;364(6444):960-965. doi: 10.1126/science.aaw7894.

Park SE1, Georgescu A1, Huh D2,3,4.

Recent studies have demonstrated an array of stem cell-derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. PMID: 31171693 DOI: 10.1126/science.aaw7894

Organoids by design

Science. 2019 Jun 7;364(6444):956-959. doi: 10.1126/science.aaw7567.

Takebe T1,2,3,4, Wells JM1,3,5.

Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organized assembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonic development and have resulted in the development of organoids with multilayer tissue complexity and higher-order functions. We discuss how the next generation of organoids can be designed by means of an engineering-based narrative design to control patterning, assembly, morphogenesis, growth, and function. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. PMID: 31171692 DOI: 10.1126/science.aaw7567



The use of brain organoids to investigate neural development and disease

Nat Rev Neurosci. 2017 Oct;18(10):573-584. doi: 10.1038/nrn.2017.107. Epub 2017 Sep 7.

Di Lullo E1,2, Kriegstein AR1,2.

Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases. PMID: 28878372 PMCID: PMC5667942 DOI: 10.1038/nrn.2017.107

Kidney Organoids: A Translational Journey

Trends Mol Med. 2017 Mar;23(3):246-263. doi: 10.1016/j.molmed.2017.01.001. Epub 2017 Feb 7.

Morizane R1, Bonventre JV2.

Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing. We summarize the current literature describing organoid studies with a special focus on kidney organoids, and discuss goals and future opportunities for organoid-based studies. Copyright © 2017 Elsevier Ltd. All rights reserved. PMID: 28188103 PMCID: PMC5442988 DOI: 10.1016/j.molmed.2017.01.001


Modeling Development and Disease with Organoids

Cell. 2016 Jun 16;165(7):1586-1597. doi: 10.1016/j.cell.2016.05.082.

Clevers H1.

Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored. Copyright © 2016 Elsevier Inc. All rights reserved. PMID: 27315476 DOI: 10.1016/j.cell.2016.05.082

Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture

PLoS One. 2016 Sep 8;11(9):e0162508. doi: 10.1371/journal.pone.0162508. eCollection 2016.

DeJonge RE1,2, Liu XP3, Deig CR1, Heller S4, Koehler KR1,2, Hashino E1,2.

Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles-a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo. PMID: 27607106 PMCID: PMC5015985 DOI: 10.1371/journal.pone.0162508