Extracellular Matrix Microstructures Modulate Hepatic Methionine Cycle and Methylations DOI
John A. Terrell, Chengpeng Chen

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

The field of mechanobiology has grown in the past decade, but limited studies investigate how extracellular matrix affects cell metabolome. methionine cycle involves catabolism and regeneration through donation recovery a single methyl group; this group can methylate DNA, RNA, proteins to alter gene expression protein-protein interactions. Through studying cells cultured on fibrous (mimicking healthy matrice (ECM)) flat severely fibrotic ECM) substrates, we observed an increase enzyme substrate. We also present is modulated by ECM transmembrane protein integrin β1. By inhibiting activation ligand-mimicking peptide RGD, that was protected from alteration. results presented provide insight into possible therapeutic targets for diseases knowledge mechanisms which alters processes.

Язык: Английский

Optogenetic control of Wnt signaling models cell-intrinsic embryogenic patterning using 2D human pluripotent stem cell culture DOI Creative Commons
Nicole Repina, Hunter J. Johnson, Xiaoping Bao

и другие.

Development, Год журнала: 2023, Номер 150(14)

Опубликована: Июль 4, 2023

ABSTRACT In embryonic stem cell (ESC) models for early development, spatially and temporally varying patterns of signaling types emerge spontaneously. However, mechanistic insight into this dynamic self-organization is limited by a lack methods spatiotemporal control signaling, the relevance signal dynamics cell-to-cell variability to pattern emergence remains unknown. Here, we combine optogenetic stimulation, imaging transcriptomic approaches study human ESCs (hESC) in two-dimensional (2D) culture. Morphogen were controlled via activation canonical Wnt/β-catenin (optoWnt), which drove broad transcriptional changes mesendoderm differentiation at high efficiency (>99% cells). When activated within subpopulations, optoWnt induced distinct epithelial mesenchymal domains, mediated migration, an mesenchymal-like transition TGFβ signaling. Furthermore, demonstrate that such subpopulations can be used uncover feedback mechanisms between neighboring types. These findings reveal Wnt sufficient generate tissue-scale patterning establish hESC model system investigating relevant embryogenesis.

Язык: Английский

Процитировано

25
Symbolic recording of signalling and cis-regulatory element activity to DNA DOI Creative Commons
Wei Chen, Junhong Choi, Xiaoyi Li

и другие.

Nature, Год журнала: 2024, Номер 632(8027), С. 1073 - 1081

Опубликована: Июль 17, 2024

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction live imaging a biological sample within timeframe interest. Here we demonstrate an alternative paradigm in which such activities stably recorded to genome. Enhancer-driven genomic recording transcriptional multiplex (ENGRAM) is based on signal-dependent production prime editing guide RNAs mediate insertion signal-specific barcodes (symbols) into genomically encoded unit. We show how this strategy can be used for cell-type-specific dozens hundreds cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging pathway-responsive elements, also time- concentration-dependent WNT, NF-κB Tet-On activities. By coupling ENGRAM sequential genome via DNA Typewriter

Язык: Английский

Процитировано

17
The evolution of developmental biology through conceptual and technological revolutions DOI Creative Commons
Prisca Liberali, Alexander F. Schier

Cell, Год журнала: 2024, Номер 187(14), С. 3461 - 3495

Опубликована: Июнь 20, 2024

Developmental biology-the study of the processes by which cells, tissues, and organisms develop change over time-has entered a new golden age. After molecular genetics revolution in 80s 90s diversification field early 21st century, we have phase when powerful technologies provide approaches open unexplored avenues. Progress has been accelerated advances genomics, imaging, engineering, computational biology emerging model systems ranging from tardigrades to organoids. We summarize how revolutionary led remarkable progress understanding animal development. describe classic questions gene regulation, pattern formation, morphogenesis, organogenesis, stem cell are being revisited. discuss connections development with evolution, self-organization, metabolism, time, ecology. speculate developmental might evolve an era synthetic biology, artificial intelligence, human engineering.

Язык: Английский

Процитировано

13
Open-top multisample dual-view light-sheet microscope for live imaging of large multicellular systems DOI Creative Commons

Franziska Moos,

Simon Suppinger, Gustavo de Medeiros

и другие.

Nature Methods, Год журнала: 2024, Номер 21(5), С. 798 - 803

Опубликована: Март 20, 2024

Abstract Multicellular systems grow over the course of weeks from single cells to tissues or even full organisms, making live imaging challenging. To bridge spatiotemporal scales, we present an open-top dual-view and dual-illumination light-sheet microscope dedicated large specimens at single-cell resolution. The configuration objectives together with a customizable multiwell mounting system combines dual view high-throughput multiposition imaging. We use this image wide variety samples highlight its capabilities gain quantitative information in such as mature intestinal organoids gastruloids.

Язык: Английский

Процитировано

12
Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking DOI
Harold M. McNamara, Sabrina C. Solley, Britt Adamson

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(11), С. 1832 - 1844

Опубликована: Окт. 2, 2024

Язык: Английский

Процитировано

11
Retinoic acid induces human gastruloids with posterior embryo-like structures DOI Creative Commons
Nobuhiko Hamazaki, Wei Yang, Connor Kubo

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(10), С. 1790 - 1803

Опубликована: Авг. 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.

Язык: Английский

Процитировано

10
Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids DOI
Simon Gsell, Sham Tlili, Matthias Merkel

и другие.

Nature Physics, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Язык: Английский

Процитировано

2
Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model DOI Creative Commons

Alba Villaronga-Luque,

Ryan Savill, Natalia López-Anguita

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

Процитировано

2
Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition DOI Creative Commons
Teresa Krammer, Hannah T. Stuart,

Elena Gromberg

и другие.

Developmental Cell, Год журнала: 2024, Номер unknown

Опубликована: Май 1, 2024

During neural tube (NT) development, the notochord induces an organizer, floorplate, which secretes Sonic Hedgehog (SHH) to pattern progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without notochord, demonstrating that can self-organize inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of marker FOXA2 was initially spatially scattered before resolving into multiple clusters, underwent competition and sorting, resulting a stable "winning" floorplate. We identified BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing receiving while simultaneously expressing BMP-inhibitor NOGGIN, promoting persistence. Noggin mutation perturbed formation NTOs vivo at mid/hindbrain regions, how autonomously notochord. Identifying pathways governing organizer is critical for harnessing developmental plasticity tissue engineering.

Язык: Английский

Процитировано

9
Three‐dimensional stem cell models of mammalian gastrulation DOI Creative Commons
David A. Turner, Alfonso Martínez Arias

BioEssays, Год журнала: 2024, Номер 46(12)

Опубликована: Авг. 28, 2024

Abstract Gastrulation is a key milestone in the development of an organism. It period cell proliferation and coordinated cellular rearrangement, that creates outline body plan. Our current understanding mammalian gastrulation has been improved by embryo culture, but there are still many open questions difficult to address because intrauterine embryos low number specimens. In case humans, additional difficulties associated with technical ethical challenges. Over last few years, pluripotent stem models being developed have potential become useful tools understand gastrulation. Here we review these special emphasis on gastruloids provide survey methods produce them robustly, their uses, relationship embryos, prospects as well limitations.

Язык: Английский

Процитировано

8