Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances DOI Creative Commons
Handuo Shi, Yi Ding,

Pingxin Sun

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 31, 2024

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers orthotopic are of great shortage. However, HTx confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs unique advantages. Small molecules promising chemical tools to modulate fate function generating high quality sources. In addition, endothelial barrier, immune responses, proliferative efficiency hepatocytes mainly contributes Interfering these biological processes is beneficial improving repopulation. this review, we will discuss applications advances in modulating differentiation reprogramming resources well its underlying mechanisms.

Language: Английский

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

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(11), P. 1832 - 1844

Published: Oct. 2, 2024

Language: Английский

Citations

11
Morphogen Patterning in Dynamic Tissues DOI Creative Commons
Alex M. Plum, Mattia Serra

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

Published: Jan. 4, 2025

Abstract Embryogenesis integrates morphogenesis—coordinated cell movements—with morphogen patterning and differentiation. While largely studied independently, morphogenesis often unfold simultaneously in early embryos. Yet, how movements affect remains unclear, as most pattern formation models assume static tissues. We address this gap by developing a mathematical framework for dynamic tissues, reformulating advection-reaction-diffusion cells’ reference frames—the natural signal interpretation fate decisions. This (i) elucidates mediates transport compartmentalization: multicellular attractors enhance cell-cell diffusive transport, while repellers act barriers, affecting induction bifurcations. (ii) It formalizes signaling ranges deconfounding morphogenetic identifying which cells can communicate. (iii) provides two nondimensional numbers—typically distinct from the Péclet number—to assess when where is relevant patterning. (iv) generative role of density dynamics apply to classic models, motifs, avian gastrulation data. Broadly, our work quantitative perspective rationalize tissue synthetic

Language: Английский

Citations

0
Neural plate pre-patterning enables specification of intermediate neural progenitors in the spinal cord DOI Creative Commons
Nagarajan Nandagopal,

Anna Cha,

Bill Jia

et al.

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

Published: Jan. 10, 2025

Summary Dorsal-ventral patterning of neural progenitors in the posterior tube, which gives rise to spinal cord, has served as a model system understand how extracellular signals organize developing tissues. While previous work shown that signaling gradients diversify progenitor fates at dorsal and ventral ends tissue, basis fate specification intermediate regions remained unclear. Here we use zebrafish investigate plate, precedes tube formation, show its pre-patterning by distinct environment enables specification. Systematic spatial analysis transcription factor (TF) expression activity using reference-based mapping approach shows plate is partitioned into striking complexity TF co-expression states that, part, correspond gastrulation such FGF Wnt persist through axis extension. Using toto cellular movement combined with mapping, find dbx1b -expressing (p0) originate from neural-plate specific state characterized transient TFs pax3a , olig4 her3 . Finally, this defined ectopic activation within pax3a/olig4 + cells sufficient promote expression. Our data broadly support occurs sequential multiple progressively tissue it develops. This implications for vitro differentiation cord cell types understanding signal-based other developmental contexts.

Language: Английский

Citations

0
Anti-resonance in developmental signaling regulates cell fate decisions DOI Creative Commons
Samuel J Rosen, Olivier Witteveen, Naomi Baxter

et al.

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

Published: Feb. 5, 2025

Cells process dynamic signaling inputs to regulate fate decisions during development. While oscillations or waves in key developmental pathways, such as Wnt, have been widely observed, the principles governing how cells decode these signals remain unclear. By leveraging optogenetic control of Wnt pathway both HEK293T and H9 human embryonic stem cells, we systematically map relationship between signal frequency downstream activation. We find that exhibit a minimal response at certain frequencies, behavior term anti-resonance. developed detailed biochemical simplified hidden variable models explain anti-resonance emerges from interplay fast slow dynamics. Remarkably, directly influences cell involved gastrulation; delivered anti-resonant frequencies result dramatically reduced mesoderm differentiation. Our work reveals previously unknown mechanism may filter against spurious These findings establish new insights into with implications for tissue engineering, regenerative medicine, cancer biology.

Language: Английский

Citations

0
Dynamical systems of fate and form in development DOI Creative Commons
Alex M. Plum, Mattia Serra

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 172, P. 103620 - 103620

Published: June 3, 2025

Developmental biology has long drawn on dynamical systems to understand the diverging fates and emerging form of developing embryo. Cell differentiation morphogenesis unfold in high-dimensional gene-expression spaces position spaces. Yet, their stable reproducible outcomes suggest low-dimensional geometric structures-e.g., fixed points, manifolds, dynamic attracting repelling structures-that organize cell trajectories both This review surveys history recent advances frameworks for development. We focus techniques extracting organizing structures fate decisions morphogenetic movements from experiments, as well interconnections. unifying, perspective aids rationalizing increasingly complex experimental datasets, facilitating principled dimensionality reduction an integrated understanding development, bridging typically distinct domains.

Language: Английский

Citations

0
Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells DOI Creative Commons

Keshi Chung,

M. F. Millet,

Ludivine Rouillon

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2262 - 2262

Published: Oct. 4, 2024

Pluripotent stem cells (PSCs) offer many potential research and clinical benefits due to their ability differentiate into nearly every cell type in the body. They are often used as model systems study early stages of ontogenesis better understand key developmental pathways, well for drug screening. However, order fully realise PSCs translational applications, a deeper understanding especially humans, is required. Several signalling molecules play important roles during development required proper differentiation PSCs. The concentration timing signal activation important, with perturbations resulting improper and/or pathology. Bone morphogenetic proteins (BMPs) one such group involved specification various types tissues human body, including those related tooth otic development. In this review, we describe role BMP its regulation, consequences dysregulation disease differentiation, how can be investigate effects modulation development, mainly focusing on Finally, emphasise unique BMP4 refined controlling regulation could lead generation more robust reproducible PSC-derived organoids applications.

Language: Английский

Citations

1
An explainable map of human gastruloid morphospace reveals gastrulation failure modes and predicts teratogens DOI Creative Commons
Joseph Rufo, Chongxu Qiu, Dasol Han

et al.

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

Published: Sept. 23, 2024

Human gastrulation is a critical stage of development where many pregnancies fail due to poorly understood mechanisms. Using the 2D gastruloid, stem cell model human gastrulation, we combined high-throughput drug perturbations and mathematical modelling create an explainable map gastruloid morphospace. This outlines patterning outcomes in response diverse identifies variations canonical failure modes. We modeled morphogen dynamics embed simulated gastruloids into experimentally-determined morphospace explain how developmental parameters drive patterning. Our predicted validated two greatest sources variance: density-based modulations Wnt signaling SOX2 stability. Assigning these as axes imparted interpretability. To demonstrate its utility, novel teratogens that zebrafish. Overall, show models can be used build comprehensive interpretable understanding set outcomes.

Language: Английский

Citations

0
Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances DOI Creative Commons
Handuo Shi, Yi Ding,

Pingxin Sun

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 31, 2024

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers orthotopic are of great shortage. However, HTx confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs unique advantages. Small molecules promising chemical tools to modulate fate function generating high quality sources. In addition, endothelial barrier, immune responses, proliferative efficiency hepatocytes mainly contributes Interfering these biological processes is beneficial improving repopulation. this review, we will discuss applications advances in modulating differentiation reprogramming resources well its underlying mechanisms.

Language: Английский

Citations

0