Cellular and molecular control of vertebrate somitogenesis

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 517 - 533

Published: Feb. 28, 2024

Language: Английский

---

Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Language: Английский

---

Modelling human brain development and disease with organoids

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

Published: Dec. 12, 2024

Language: Английский

---

Retinoic acid induces human gastruloids with posterior embryo-like structures

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1790 - 1803

Published: Aug. 20, 2024

Abstract Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed all three germ layers, gastruloids do not morphologically resemble post-implantation embryos. Here we show that an pulse retinoic acid (RA), together with later Matrigel, robustly induces posterior embryo-like morphological structures, including neural tube flanked by segmented somites diverse cell types, crest, progenitors, renal progenitors myocytes. Through silico staging based on single-cell RNA sequencing, find RA-gastruloids progress further than other or mouse embryo models, aligning to E9.5 CS11 cynomolgus monkey We leverage chemical genetic perturbations confirm WNT BMP signalling regulate somite formation length the context, while transcription factors TBX6 PAX3 underpin presomitic mesoderm respectively. Looking forward, robust, scalable for decoding embryogenesis.

Language: Английский

---

From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human biomedical research. In response to this demand, organoids and organ chips were integrated greater physiological relevance dynamic, controlled experimental conditions. This innovative platform—the organoids-on-a-chip technology—shows great promise disease modeling, discovery, personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, industry stakeholders. review traces evolution organoids-on-a-chip, driven by necessity advanced biological models. We summarize applications of simulating pathological phenotypes therapeutic evaluation technology. section highlights how integrating technologies chips, such as microfluidic systems, mechanical stimulation, sensor integration, optimizes organoid cell types, spatial structure, functions, thereby expanding their applications. conclude addressing current challenges offering insights into prospects. advancement is poised enhance fidelity, standardization, scalability. Furthermore, integration cutting-edge interdisciplinary collaborations will be crucial progression

Language: Английский

---

Advances in Spatial Omics Technologies

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Rapidly developing spatial omics technologies provide us with new approaches to deeply understanding the diversity and functions of cell types within organisms. Unlike traditional approaches, enable researchers dissect complex relationships between tissue structure function at cellular or even subcellular level. The application provides perspectives on key biological processes such as nervous system development, organ tumor microenvironment. This review focuses advancements strategies technologies, summarizes their applications in biomedical research, highlights power advancing life sciences related development disease.

Language: Английский

---

Pluripotent cell states and fates in human embryo models

Development, Journal Year: 2025, Volume and Issue: 152(7)

Published: April 1, 2025

ABSTRACT Pluripotency, the capacity to generate all cells of body, is a defining property transient population epiblast found in pre-, peri- and post-implantation mammalian embryos. As development progresses, undergo dynamic transitions pluripotency states, concurrent with specification extra-embryonic embryonic lineages. Recently, stem cell-based models pre- human have been developed using that capture key properties at different developmental stages. Here, we review early primate development, comparing states vivo cultured pluripotent representative these states. We consider how status starting influences embryo and, turn, what can learn about epiblast. Finally, discuss limitations questions arising from pioneering studies this emerging field.

Language: Английский

---

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(5), P. 3203 - 3217

Published: April 1, 2024

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment in vitro models for cord-related diseases highly challenging. Currently, both vivo are still underdeveloped, complicating exploration development effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable diseases. However, cultivation organoids predominantly relies on Matrigel, a matrix derived murine sarcoma tissue. Tissue-specific extracellular matrices key drivers complex organ development, thus underscoring urgent need to research safer more physiologically relevant organoid culture materials. Herein, we have prepared rat decellularized brain hydrogel (DBECMH), which supports formation hiPSC-derived organoids. Compared with DBECMH exhibited higher expression levels markers multiple compartments natural cord, facilitating maturation tissues. Our study suggests that holds potential replace Matrigel standard medium organoids, thereby advancing protocols their application modeling

Language: Английский

---

Toward developing human organs via embryo models and chimeras

Cell, Journal Year: 2024, Volume and Issue: 187(13), P. 3194 - 3219

Published: June 1, 2024

Developing functional organs from stem cells remains a challenging goal in regenerative medicine. Existing methodologies, such as tissue engineering, bioprinting, and organoids, only offer partial solutions. This perspective focuses on two promising approaches emerging for engineering human cells: cell-based embryo models interspecies organogenesis. Both exploit the premise of guiding to mimic natural development. We begin by summarizing what is known about early development blueprint recapitulating organogenesis both chimeras. The latest advances fields are discussed before highlighting technological knowledge gaps be addressed developing could achieved using approaches. conclude discussing challenges facing modeling outlining future prospects advancing toward generation tissues basic research translational applications.

Language: Английский

---

Advances in the Generation of Constructed Cardiac Tissue Derived from Induced Pluripotent Stem Cells for Disease Modeling and Therapeutic Discovery

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 250 - 250

Published: Jan. 29, 2024

The human heart lacks significant regenerative capacity; thus, the solution to failure (HF) remains organ donation, requiring surgery and immunosuppression. demand for constructed cardiac tissues (CCTs) model treat disease continues grow. Recent advances in induced pluripotent stem cell (iPSC) manipulation, CRISPR gene editing, 3D tissue culture have enabled a boom iPSC-derived CCTs (iPSC-CCTs) with diverse types architecture. Compared 2D-cultured cells, iPSC-CCTs better recapitulate biology, demonstrating potential advance modeling, drug discovery, medicine, though could benefit from methods faithfully mimic physiology electrophysiology. Here, we summarize future developments vascularization, immunization, maturation of study therapy.

Language: Английский

---