Emerging approaches to enhance human brain organoid physiology DOI Creative Commons
Anna Pagliaro, Benedetta Artegiani, Delilah Hendriks

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.

Language: Английский

Human fetal brain self-organizes into long-term expanding organoids DOI Creative Commons
Delilah Hendriks, Anna Pagliaro, Francesco Andreatta

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 712 - 732.e38

Published: Jan. 8, 2024

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, solely established pluripotent stem cells. Here, we show that healthy human fetal in vitro self-organizes into (FeBOs), phenocopying aspects of vivo cellular heterogeneity and complex organization. FeBOs expanded over long time periods. FeBO growth requires maintenance integrity, which ensures production tissue-like extracellular matrix (ECM) niche, ultimately endowing expansion. lines derived different areas the central nervous system (CNS), including dorsal ventral forebrain, preserve their regional identity allow probe positional identity. Using CRISPR-Cas9, showcase generation syngeneic mutant for study cancer. Taken together, constitute complementary CNS organoid platform.

Language: Английский

Citations

40

Human assembloids reveal the consequences of CACNA1G gene variants in the thalamocortical pathway DOI
Ji‐il Kim, Yuki Miura, Min-Yin Li

et al.

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

18

Rigor and reproducibility in human brain organoid research: Where we are and where we need to go DOI Creative Commons
Soraya O. Sandoval, Gerarda Cappuccio, Karina Kruth

et al.

Stem Cell Reports, Journal Year: 2024, Volume and Issue: 19(6), P. 796 - 816

Published: May 16, 2024

Human brain organoid models have emerged as a promising tool for studying human development and function. These preserve genetics recapitulate some aspects of development, while facilitating manipulation in an vitro setting. Despite their potential to transform biology medicine, concerns persist about fidelity. To fully harness potential, it is imperative establish reliable analytic methods, ensuring rigor reproducibility. Here, we review current analytical platforms used characterize forebrain cortical organoids, highlight challenges, propose recommendations future studies achieve greater precision uniformity across laboratories.

Language: Английский

Citations

14

Assembloid models of cell-cell interaction to study tissue and disease biology DOI
Massimo M. Onesto, Ji‐il Kim, Sergiu P. Paşca

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(11), P. 1563 - 1573

Published: Oct. 24, 2024

Language: Английский

Citations

12

Organoid-guided precision hepatology for metabolic liver disease DOI
Sho Osonoi, Takanori Takebe

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(5), P. 805 - 821

Published: Jan. 17, 2024

Language: Английский

Citations

11

Modelling human brain development and disease with organoids DOI
Marcella Birtele, Madeline A. Lancaster, Giorgia Quadrato

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Language: Английский

Citations

11

Spatially Resolved in vivo CRISPR Screen Sequencing via Perturb-DBiT DOI Creative Commons
Alev Baysoy, Xiaolong Tian, Feifei Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Perturb-seq enabled the profiling of transcriptional effects genetic perturbations in single cells but lacks ability to examine impact on tissue environments. We present Perturb-DBiT for simultaneous co- sequencing spatial transcriptome and guide RNAs (gRNAs) same section vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding how modifications affect cellular behavior architecture. This platform supports variety delivery vectors, library sizes, preparations, along two distinct capture methods, making it adaptable wide range experimental setups. In applying Perturb-DBiT, we conducted un-biased knockouts tens genes or at genome-wide scale across three cancer models. mapped all gRNAs individual colonies corresponding transcriptomes human metastatic colonization model, revealing clonal dynamics cooperation. also examined effect perturbation tumor immune microenvironment an immune-competent syngeneic uncovering differential synergistic promoting infiltration suppression tumors. allows simultaneously evaluating each knockout initiation, development, metastasis, histopathology, landscape. Ultimately, not only broadens scope inquiry, lays groundwork developing targeted therapeutic strategies.

Language: Английский

Citations

10

Functional neurogenomics in autism spectrum disorders: A decade of progress DOI
Lucy Bicks, Daniel H. Geschwind

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 86, P. 102858 - 102858

Published: March 27, 2024

Language: Английский

Citations

9

Engineering brain-on-a-chip platforms DOI
Bram Servais, Negar Mahmoudi, Vini Gautam

et al.

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(8), P. 691 - 709

Published: June 5, 2024

Language: Английский

Citations

9

3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling DOI

Tong Zhu,

Yan Hu, Haitao Cui

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Cell spheroids (esp. organoids) as 3D culture platforms are popular models for representing cell–cell and cell–extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures natural tissues. with spatially organized multiple types preferred gaining comprehensive insights into tissue pathophysiology constructing in vitro tissues disease because of complexities In recent years, an assembly strategy using (or living building blocks has been developed to construct complex spatial organization. Here, a overview advances multispheroid studies is provided. The different mechanisms techniques, i.e., automated directed assembly, noncontact remote programmed self‐assembly, introduced. processing steps, advantages, technical limitations existing methodologies summarized. Applications strategies modeling, drug screening, engineering, organogenesis reviewed. Finally, this review concludes by emphasizing persistent issues future perspectives, encouraging researchers adopt techniques generating advanced that better resemble real

Language: Английский

Citations

9