Phospho-seq: integrated, multi-modal profiling of intracellular protein dynamics in single cells DOI Creative Commons
John D. Blair, Austin Hartman, Fides Zenk

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Language: Английский

Robust phenotyping of highly multiplexed tissue imaging data using pixel-level clustering DOI Creative Commons
Candace C. Liu, Noah F. Greenwald,

Alex Kong

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 1, 2023

Abstract While technologies for multiplexed imaging have provided an unprecedented understanding of tissue composition in health and disease, interpreting this data remains a significant computational challenge. To understand the spatial organization how it relates to disease processes, studies typically focus on cell-level phenotypes. However, images can capture biologically important objects that are outside cells, such as extracellular matrix. Here, we describe pipeline, Pixie, achieves robust quantitative annotation pixel-level features using unsupervised clustering show its application across variety biological contexts platforms. Furthermore, current cell phenotyping strategies rely be labor intensive require large amounts manual cluster adjustments. We demonstrate pixel clusters lie within cells used improve annotations. comprehensively evaluate pre-processing steps parameter choices optimize performance quantify reproducibility our method. Importantly, Pixie is open source easily customizable through user-friendly interface.

Language: Английский

Citations

51

Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications DOI
Sushila Maharjan,

Chenshuo Ma,

Bibhor Singh

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 208, P. 115237 - 115237

Published: March 5, 2024

Language: Английский

Citations

27

Establishing a conceptual framework for holistic cell states and state transitions DOI Creative Commons
Susanne M. Rafelski, Julie A. Theriot

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2633 - 2651

Published: May 1, 2024

Cell states were traditionally defined by how they looked, where located, and what functions performed. In this post-genomic era, the field is largely focused on a molecular view of cell state. Moving forward, we anticipate that observables used to define will evolve again as single-cell imaging analytics are advancing at breakneck pace via collection large-scale, systematic image datasets application quantitative image-based data science methods. This is, therefore, key moment in arc biological research develop approaches integrate spatiotemporal physical structure organization with toward concept holistic perspective, propose conceptual framework for state transitions data-driven, practical, useful enable integrative analyses modeling across many types.

Language: Английский

Citations

24

Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery DOI Creative Commons
Junxian Cao, Caifeng Li,

Zhao Cui

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2946 - 2968

Published: Jan. 1, 2024

Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy accelerating discovery process. With evolution spatial (ST) technology emerged as a derivative approach. Spatial hot topic field omics research recent years; it not only provides information on gene expression levels but also offers expression. This shown tremendous potential disease understanding In this article, we introduce analytical strategies review its applications novel target mechanism unravelling. Moreover, discuss current challenges issues that need be addressed. conclusion, new perspective

Language: Английский

Citations

16

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium DOI Creative Commons
Jonathan R. Soucy,

Erika A. Aguzzi,

Julie Cho

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Sept. 21, 2023

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach reverse from if newly introduced neurons can reestablish functional retinal thalamic circuits. In theory, RGCs might be repopulated through transplantation of stem cell-derived or via induction endogenous transdifferentiation. The Repopulation, Stem Cell Transplantation, Optic Nerve Regeneration (RReSTORe) Consortium was established address challenges associated with repair visual pathway neuropathy. 2022, RReSTORe initiated ongoing international collaborative discussions advance field has identified five critical areas focus: (1) development differentiation, (2) Transplantation methods models, (3) survival, maturation, host interactions, (4) Inner wiring, (5) Eye-to-brain connectivity. Here, we discuss most pertinent questions that exist on path clinical translation suggest experimental directions propel this work going forward. Using these subtopic discussion groups (SDGs) as framework, multidisciplinary approaches restore diseased by leveraging groundbreaking insights developmental neuroscience, biology, molecular optical imaging, animal models neuropathy, immunology & immunotolerance, neuropathology neuroprotection, materials science biomedical engineering, neuroscience. While significant hurdles remain, Consortium's efforts provide comprehensive roadmap for advancing hold potential transformative progress restoring patients suffering neuropathies.

Language: Английский

Citations

36

Middle-out methods for spatiotemporal tissue engineering of organoids DOI Open Access
Michael R. Blatchley, Kristi S. Anseth

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(5), P. 329 - 345

Published: March 13, 2023

Language: Английский

Citations

30

Replacing Animal Testing with Stem Cell-Organoids : Advantages and Limitations DOI Creative Commons

G Park,

Yeri Alice Rim,

Yeowon Sohn

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(6), P. 1375 - 1386

Published: April 19, 2024

Various groups including animal protection organizations, medical research centers, and even federal agencies such as the U.S. Food Drug Administration, are working to minimize use in scientific experiments. This movement primarily stems from welfare ethical concerns. However, recent advances technology new studies medicine have contributed an increase experiments throughout years. With rapid testing, concerns arise issues, high cost, complex procedures, potential inaccuracies.Alternative solutions recently been investigated address problems of testing. Some these technologies related stem cell technologies, organ-on-a-chip, organoids, induced pluripotent models. The aim review is focus on methodologies, that can serve alternative testing discuss its advantages limitations, alongside regulatory considerations.Although methodologies has shortcomings, it replace Achieving this requires further cells, with societal technological benefits.

Language: Английский

Citations

15

A highly reproducible and efficient method for retinal organoid differentiation from human pluripotent stem cells DOI Creative Commons
Jade Harkin,

Kiersten H. Peña,

Cátia Gomes

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 13, 2024

Human pluripotent stem cell (hPSC)-derived retinal organoids are three-dimensional cellular aggregates that differentiate and self-organize to closely mimic the spatial temporal patterning of developing human retina. Retinal organoid models serve as reliable tools for studying retinogenesis, yet limitations in efficiency reproducibility current differentiation protocols have reduced use these more high-throughput applications such disease modeling drug screening. To address shortcomings, study aimed standardize prior yield a highly reproducible efficient method generating organoids. Results demonstrated through regulation size shape using quick reaggregation methods, were compared traditional methods. Additionally, timed activation BMP signaling within cells generated pure populations at 100% from multiple widely used lines, with default forebrain fate resulting inhibition signaling. Furthermore, given ability direct or fates complete purity, mRNA-seq analyses then utilized identify some earliest transcriptional changes occur during specification two lineages common progenitor. These improved methods also yielded expedited timelines when Taken together, results this demonstrate development minimally variable suitable analyzing stages specification.

Language: Английский

Citations

14

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

Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems DOI Creative Commons
Fides Zenk, Jonas Simon Fleck, Sophie Jansen

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(7), P. 1376 - 1386

Published: June 24, 2024

Abstract Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate restriction. Unveiling the epigenetic mechanisms underlying diversity has been difficult. In this study, we use brain and retina organoid models present single-cell profiling H3K27ac, H3K27me3 H3K4me3 histone from progenitor to differentiated neural fates reconstruct epigenomic trajectories regulating identity acquisition. We capture transitions pluripotency through neuroepithelium retinal region type specification. Switching repressive activating can precede predict decisions at each stage, providing a temporal census gene regulatory elements transcription factors. Removing neuroectoderm stage disrupts restriction, aberrant Our epigenome-wide map development serves as blueprint explore determination.

Language: Английский

Citations

11