Theriogenology, Год журнала: 2021, Номер 180, С. 189 - 206
Опубликована: Дек. 23, 2021
Язык: Английский
WIREs Mechanisms of Disease, Год журнала: 2022, Номер 14(4)
Опубликована: Фев. 9, 2022
Abstract The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting canonical FGFs and endocrine that activate four receptor tyrosine kinases (FGFRs 1–4) intracellular (intracellular or iFGFs) primarily function to regulate the activity voltage‐gated sodium channels other molecules. FGFs, iFGFs have been reviewed extensively by us others. In this review, we briefly summarize past reviews then focus on new developments in FGF field since our last review 2015. Some highlights 6 years include use optogenetic tools, viral vectors, inducible transgenes experimentally modulate signaling, clinical small molecule FGFR inhibitors, an expanded understanding functions for stem cell pluripotency differentiation, roles tissue homeostasis regeneration, a continuing elaboration mechanisms development, expanding appreciation neuropsychiatric diseases. This article categorized under: Cardiovascular Diseases > Molecular Cellular Physiology Neurological Congenital Stem Cells Development Cancer
Язык: Английский
Процитировано
99
Developmental Cell, Год журнала: 2020, Номер 55(3), С. 341 - 353.e5
Опубликована: Окт. 21, 2020
Язык: Английский
Процитировано
85
eLife, Год журнала: 2020, Номер 9
Опубликована: Июль 27, 2020
Precise control and maintenance of population size is fundamental for organismal development homeostasis. The three cell types the mammalian blastocyst are generated in precise proportions over a short time, suggesting mechanism to ensure reproducible outcome. We developed minimal mathematical model demonstrating growth factor signaling sufficient guarantee this robustness which anticipates an embryo's response perturbations lineage composition. Addition lineage-restricted cells both vivo silico, causes shift fate progenitors away from supernumerary type, while eliminating using laser ablation biases specification toward targeted type. Finally, FGF4 couples decisions composition through changes local concentration, providing basis regulative abilities early embryo whereby coordinated at level robustly generate tissues right proportions.
Язык: Английский
Процитировано
74
Biochemical Journal, Год журнала: 2023, Номер 480(23), С. 1909 - 1928
Опубликована: Дек. 1, 2023
Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address question how ERK exerts distinct context-specific effects on multiple processes. We discuss dynamics activity induce selective changes in gene expression programs, with insights from both experiments computational models. With focus single-cell biosensor-based studies, summarize four major functional modes for signaling tissues: adjusting size populations, gradient-based patterning, wave propagation morphological changes, diversification states. These operation are disrupted cancer other related diseases represent potential targets therapeutic intervention. By understanding dynamic mechanisms involved signaling, there is pharmacological strategies that not only simply inhibit ERK, but also restore patterns improve disease outcomes.
Язык: Английский
Процитировано
20
Development, Год журнала: 2022, Номер 149(4)
Опубликована: Фев. 15, 2022
Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the activity signaling network in at high time resolution. Here, we use live sensors wild-type Fgf4-mutant mouse embryonic stem measure ERK single cells, for defined ligand concentrations states. These reveal pulses activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become prevalent with higher concentration, but rarer differentiated Our results suggest that operates vicinity transition point oscillatory non-oscillatory dynamics resulting add new dimension cellular heterogeneity may be linked divergent cultures.
Язык: Английский
Процитировано
26
Development, Год журнала: 2022, Номер 149(20)
Опубликована: Авг. 22, 2022
Embryogenesis is supported by dynamic loops of cellular interactions. Here, we create a partial mouse embryo model to elucidate the principles epiblast (Epi) and extra-embryonic endoderm co-development (XEn). We trigger naive embryonic stem cells form blastocyst-stage niche Epi-like XEn-like (3D, hydrogel free serum free). Once established, these two lineages autonomously progress in minimal medium an inner pro-amniotic-like cavity surrounded polarized covered with visceral (VE)-like cells. The progression occurs through reciprocal inductions which Epi supports primitive (PrE) produce basal lamina that subsequently regulates polarization and/or cavitation, which, return, channels transcriptomic VE. This VE then contributes bifurcation into anterior- posterior-like states. Similarly, boosting formation PrE-like within blastoids developmental progression. argue self-organization can arise from lineage followed pendulum induction propagates over time.
Язык: Английский
Процитировано
20
Development, Год журнала: 2024, Номер 151(8)
Опубликована: Апрель 2, 2024
The lineage decision that generates the epiblast and primitive endoderm from inner cell mass (ICM) is a paradigm for fate specification. Recent mathematics has formalized Waddington's landscape metaphor proven decisions in detailed gene network models must conform to small list of low-dimensional stereotypic changes called bifurcations. most plausible bifurcation ICM so-called heteroclinic flip we define elaborate here. Our re-analysis recent data suggests there sufficient movement so FGF signal, which drives decision, can be treated as spatially uniform. We thus extend model single entire by means self-consistently defined time-dependent signal. This consistent with available propose additional dynamic experiments test it further. demonstrates simplified, quantitative intuitively transparent descriptions are possible when attention shifted specific genes lineages. very any situation where embryo needs control over relative proportions two fates morphogen feedback.
Язык: Английский
Процитировано
5
Materials Advances, Год журнала: 2024, Номер 5(11), С. 4772 - 4785
Опубликована: Янв. 1, 2024
The molecular layer that adsorbs on the biomaterial surface upon contacting body tissues and fluids, termed conditioning (CL), influences cell behavior regulating scaffold integration resilience in a patient-specific fashion.
Язык: Английский
Процитировано
4
Cell Proliferation, Год журнала: 2023, Номер 56(6)
Опубликована: Янв. 2, 2023
The pluripotent stem cells exist in a narrow window during early development and its derivation depends on intrinsic extrinsic growth signalling vitro. It has remained challenging to derive two or three distinct cell lines that are representative of blastocyst-stage lineages from one preimplantation embryo simultaneously chemical defined condition. Therefore, it is desirable establish system by manipulating culture multiple types single blastocyst. This study used medium containing Activin A, WNT activator LIF (ACL medium), enabling establishment ACL-ESCs ACL-XEN ACL-blastoids were generated suspending with ACL-blastoid three-dimensional system. Lineage markers expression performed immunofluorescence. Our results indicate derived blastocyst represent ICM PrE lineages. Importantly, we obtained self-aggregation, partially recapitulating initiation implantation events. would not only provide ACL for maintenance corresponding as well PrE, but also reconstruct blastoids them deepen our understanding embryogenesis widen insights into translational application cells.
Язык: Английский
Процитировано
9
Nature Chemical Biology, Год журнала: 2023, Номер 19(5), С. 596 - 606
Опубликована: Янв. 12, 2023
Abstract Cells can secrete molecules that help each other’s replication. In cell cultures, chemical signals might diffuse only within a colony or between colonies. A signal’s interaction length—how far apart interacting cells are—is often assumed to be some value without rigorous justifications because molecules’ invisible paths and complex multicellular geometries pose challenges. Here we present an approach, combining mathematical models experiments, for determining length. With murine embryonic stem (ES) as testbed, found differentiating ES FGF4, among others, communicate over many millimeters in culture dishes and, thereby, form spatially extended, macroscopic entity grows if its centimeter-scale population density is above threshold value. this ‘macroscopic quorum sensing’, isolated macroscopic, but not microscopic, survive differentiation. Our integrated approach determine signals’ lengths generic communities.
Язык: Английский
Процитировано
9