Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans DOI Creative Commons
Yi Zhou, Yijing Su, Qian Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, mice showed few shared (such as DPYSL5), mostly species-specific gene expression that converged onto common biological processes regulating development. We further human-specific transcriptomic demonstrated functional roles human imGC-enriched a family proton-transporting vacuolar-type ATPase subtypes development derived pluripotent stem cells. study reveals divergent patterns convergent the molecular characteristics species, highlighting importance conducting independent analyses for different species.

Language: Английский

Organoids: The current status and biomedical applications DOI Creative Commons
Siqi Yang, Hai‐Jie Hu, Heng‐Chung Kung

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 17, 2023

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that derived from cells with stem potential and can self-organize differentiate into 3D cell masses, recapitulating the morphology functions their in vivo counterparts. Organoid culture is an emerging technology, organoids various tissues, such as brain, lung, heart, liver, kidney, have been generated. Compared traditional bidimensional culture, organoid systems unique advantage conserving parental gene expression mutation characteristics, well long-term maintenance function biological characteristics vitro. All these features open up new opportunities for drug discovery, large-scale screening, precision medicine. Another major application disease modeling, especially hereditary diseases difficult to model vitro modeled by combining genome editing technologies. Herein, we introduce development current advances technology field. We focus on applications basic biology clinical research, also highlight limitations future perspectives. hope this review provide a valuable reference developments organoids.

Language: Английский

Citations

105
Genetics of human brain development DOI
Yi Zhou, Hongjun Song, Guo‐li Ming

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

Citations

69
Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoid transplanted in mouse brain DOI
Meiyan Wang, Lei Zhang, Sammy Weiser Novak

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 28, 2024

Language: Английский

Citations

30
Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids DOI
Zheng Sun,

Zhenni Chen,

Man Yin

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 772 - 787.e11

Published: April 1, 2024

Language: Английский

Citations

19
Brain organoid protocols and limitations DOI Creative Commons
Helen Zhao, Gabriel G. Haddad

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 20, 2024

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends scope our understanding human biology diseases. Brain organoids especially open an opportunity for brain modeling many neurological diseases, which have lagged due to inaccessibility samples lack similarity with other animal models. can be generated through various protocols mimic whole or region-specific. To provide overview technology, we summarize currently available list several factors consider before choosing protocols. We also outline limitations current challenges need solved in future investigation development pathobiology.

Language: Английский

Citations

15
Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction DOI Creative Commons
Hairong Jin, Zengqi Xue, Jinnv Liu

et al.

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

Tissue damage and functional abnormalities in organs have become a considerable clinical challenge. Organoids are often applied as disease models drug discovery screening. Indeed, several studies shown that organoids an important strategy for achieving tissue repair biofunction reconstruction. In contrast to established stem cell therapies, high relevance. However, conventional approaches limited the application of regenerative medicine. Engineered might capacity overcome these challenges. Bioengineering—a multidisciplinary field applies engineering principles biomedicine—has bridged gap between medicine promote human health. More specifically, bioengineering been accelerate their translation. this review, beginning with basic concepts organoids, we describe strategies cultivating engineered discuss multiple modes create conditions breakthroughs organoid research. Subsequently, on reconstruction presented. Finally, highlight limitations challenges hindering utilization applications. Future research will focus using advanced tools personalized

Language: Английский

Citations

12
Effective cryopreservation of human brain tissue and neural organoids DOI Creative Commons
Weiwei Xue, Huijuan Li,

XU Jin-hong

et al.

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(5), P. 100777 - 100777

Published: May 1, 2024

Human brain tissue models and organoids are vital for studying modeling human neurological disease. However, the high cost of long-term cultured inhibits their wide-ranging application. It is therefore urgent to develop methods cryopreservation organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, Y27632 (termed MEDY) cortical without disrupting neural cytoarchitecture or functional activity. MEDY can be applied multiple brain-region-specific organoids, including dorsal/ventral forebrain, spinal cord, optic vesicle brain, epilepsy patient-derived Additionally, enables samples, pathological features retained after thawing. Transcriptomic analysis shows that protect synaptic function inhibit endoplasmic reticulum-mediated apoptosis pathway. will enable large-scale reliable storage diverse living facilitate research, medical applications, drug screening.

Language: Английский

Citations

11
Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts DOI Creative Commons
Yu Tan,

Robert C. Coyle,

Ryan W. Barrs

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(31)

Published: Aug. 4, 2023

Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell–derived cardiomyocyte (hPSC-CM) transplantation. Here, we show engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated biocompatibility e-SiNWs their capacity improve microtissue engraftment in healthy rat myocardium. Nanowired were then hPSC-CMs, nonmyocyte supporting cells, e-SiNWs. Nonmyocyte cells promoted greater ischemia tolerance organoids, improved electrical pacing capacity. After transplantation into ischemia/reperfusion–injured hearts, nanowired contractile development engrafted induced potent functional recovery, reduced maladaptive left ventricular remodeling. Compared contemporary studies an identical injury model, recovery was achieved a 20-fold lower dose revealing synergy between nanomaterials efficient heart repair.

Language: Английский

Citations

21
Human iPSC-derived cell grafts promote functional recovery by molecular interaction with stroke-injured brain DOI Creative Commons
R. Weber, Beatriz Achón Buil, Nora H. Rentsch

et al.

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

Published: April 5, 2024

Abstract Stroke is a leading cause of disability and death due to the brain’s limited ability regenerate damaged neural circuits. To date, stroke patients have only few therapeutic options are often left with considerable disabilities. Induced pluripotent stem cell (iPSC)-based therapies emerging as promising approach for recovery. In this study, we demonstrate that local transplantation good manufacturing practice (GMP)-compatible iPSC-derived progenitor cells (NPCs) improve long-term recovery-associated brain tissue responses reduce neurological deficits after cerebral ischemia in mice. Using vivo bioluminescence imaging post-mortem histology, showed graft survival over course five weeks preferential differentiation into mature neurons without signs residuals. Transplantation NPCs led set including increased vascular sprouting repair, improved blood-brain barrier integrity, reduced microglial activation, neurogenesis compared littermate control animals receiving sham transplantation. Employing deep learning-assisted behavior analysis, found NPC-treated mice displayed gait performance complete fine-motor recovery horizontal ladder rung walk, post-injury. dissect molecular composition identify graft-host interactions, single nucleus profiling transplants host was performed. We identified preferentially towards GABAergic remaining acquiring glutamatergic neuron, astrocyte, NPC-like phenotypes. Interaction between transcriptome indicated grafts were primarily involved communication through regeneration-associated NRXN, NRG, NCAM SLIT signalling pathways. conclusion, our study reveals transplanted differentiate contributing recovery, further delineates regenerative interactions stroke-injured tissue.

Language: Английский

Citations

8
Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain DOI Creative Commons

Katherine Boylin,

Grace V. Aquino,

Michael Purdon

et al.

Biofabrication, Journal Year: 2024, Volume and Issue: 16(3), P. 032007 - 032007

Published: May 15, 2024

Abstract Understanding the complexities of human brain’s function in health and disease is a formidable challenge neuroscience. While traditional models like animals offer valuable insights, they often fall short accurately mirroring biology drug responses. Moreover, recent legislation has underscored need for more predictive that represent physiology. To address this requirement, human-derived cell cultures have emerged as crucial alternative biomedical research. However, static culture lack dynamic tissue microenvironment governs function. Advanced vitro systems, such organoids microphysiological systems (MPSs), bridge gap by offering accurate representations biology. Organoids, which are three-dimensional miniaturized organ-like structures derived from stem cells, exhibit physiological responses akin to native tissues, but essential tissue-specific components functional vascular immune cells. Recent endeavors focused on incorporating endothelial cells into enhance vascularization, maturation, modeling. MPS, including organ-on-chip technologies, integrate diverse types vascularization under conditions, revolutionizing brain research bridging between vivo models. In review, we delve evolution with particular focus highlighting significance enhancing viability, functionality, modeling potential organoids. By examining interplay vasculature neuronal within organoids, can uncover novel therapeutic targets gain insights mechanisms, promise significant advancements neuroscience improved patient outcomes.

Language: Английский

Citations

8