Efficient Reprogramming of Mouse Embryonic Stem Cells into Trophoblast Stem-like Cells via Lats Kinase Inhibition DOI Creative Commons
Yake Gao,

Wenrui Han,

Rui Dong

и другие.

Biology, Год журнала: 2024, Номер 13(2), С. 71 - 71

Опубликована: Янв. 24, 2024

Mouse zygotes undergo multiple rounds of cell division, resulting in the formation preimplantation blastocysts comprising three lineages: trophectoderm (TE), epiblast (EPI), and primitive endoderm (PrE). Cell fate determination plays a crucial role establishing healthy pregnancy. The initial separation lineages gives rise to TE inner mass (ICM), from which trophoblast stem cells (TSC) embryonic (ESC) can be derived vitro. Studying lineage differentiation is greatly facilitated by clear functional distinction between TSC ESC. However, transitioning these two types naturally poses challenges. In this study, we demonstrate that inhibiting LATS kinase promotes conversion ICM also effectively reprograms ESC into stable, self-renewing TS-like (TSLC). Compared TSC, TSLC exhibits similar molecular properties, including high expression marker genes such as Cdx2, Eomes, Tfap2c, well hypomethylation their promoters. Importantly, not only displays ability differentiate mature vitro but participates placenta vivo. These findings highlight efficient reprogramming ESCs TSLCs using small inducer, provides new reference for understanding regulatory network TSCs.

Язык: Английский

Substratum stiffness regulates Erk signaling dynamics through receptor-level control DOI Creative Commons
Payam E. Farahani, Sandra B. Lemke, Elliot Dine

и другие.

Cell Reports, Год журнала: 2021, Номер 37(13), С. 110181 - 110181

Опубликована: Дек. 1, 2021

The EGFR/Erk pathway is triggered by extracellular ligand stimulation, leading to stimulus-dependent dynamics of activity. Although mechanical properties the microenvironment also affect Erk activity, their effects on signaling are poorly understood. Here, we characterize how stiffness underlying substratum affects in mammary epithelial cells. We find that soft microenvironments attenuate signaling, both at steady state and response epidermal growth factor (EGF) stimulation. Optogenetic manipulation multiple nodes reveals intracellular signal transmission largely unaffected stiffness. Instead, decrease EGF receptor (EGFR) expression alter amount spatial distribution binding cell membranes. Our data demonstrate tunes via receptor-ligand interactions, underscoring microenvironmental signals jointly processed through a highly conserved regulates tissue development, homeostasis, disease progression.

Язык: Английский

Процитировано

41
Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells DOI Creative Commons
Dhruv Raina, Fiorella Fabris, Luis G. Morelli

и другие.

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
A guide to ERK dynamics, part 1: mechanisms and models DOI Creative Commons
Abhineet Ram,

Devan Murphy,

Nicholaus DeCuzzi

и другие.

Biochemical Journal, Год журнала: 2023, Номер 480(23), С. 1887 - 1907

Опубликована: Дек. 1, 2023

Extracellular signal-regulated kinase (ERK) has long been studied as a key driver of both essential cellular processes and disease. A persistent question how this single pathway is able to direct multiple cell behaviors, including growth, proliferation, death. Modern biosensor studies have revealed that the temporal pattern ERK activity highly variable heterogeneous, critically, these dynamic differences modulate fate. This two-part review discusses current understanding in pathway, it regulates decisions, fates lead tissue regulation pathology. In part 1, we cover optogenetic live-cell imaging technologies first nature ERK, well challenges data analysis. We also discuss advances mathematical models for mechanisms dynamics, receptor-level regulation, negative feedback, cooperativity, paracrine signaling. While hurdles still remain, clear higher spatial resolution provide mechanistic insights into circuitry. Exciting new algorithms advanced computational tools enable quantitative measurements single-cell activation, which turn inform better behavior. However, fact cannot fully recapitulate diversity responses calls deeper network structure signal transduction general.

Язык: Английский

Процитировано

17
Molecular versatility during pluripotency progression DOI Creative Commons

Giacomo Furlan,

Aurélia Huyghe, Noémie Combémorel

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 5, 2023

A challenge during development is to ensure lineage segregation while preserving plasticity. Using pluripotency progression as a paradigm, we review how developmental transitions are coordinated by redeployments, rather than global resettings, of cellular components. We highlight changes in response extrinsic cues (FGF, WNT, Activin/Nodal, Netrin-1), context- and stoichiometry-dependent action transcription factors (Oct4, Nanog) reconfigurations epigenetic regulators (enhancers, promoters, TrxG, PRC) may confer robustness naïve primed transition. propose the notion Molecular Versatility regroup mechanisms which molecules repurposed exert different, sometimes opposite, functions close stem cell configurations.

Язык: Английский

Процитировано

14
Optogenetic manipulation identifies the roles of ERK and AKT dynamics in controlling mouse embryonic stem cell exit from pluripotency DOI Creative Commons
Geethika Arekatla, Christoph Trenzinger,

Andreas Reimann

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(12), С. 1022 - 1036.e4

Опубликована: Май 18, 2023

Язык: Английский

Процитировано

12
A Spatiotemporal Compartmentalization of Glucose Metabolism Guides Mammalian Gastrulation Progression DOI Creative Commons
Dominica Cao, Liangwen Zhong, Anupama Hemalatha

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 7, 2023

Gastrulation is considered the

Язык: Английский

Процитировано

12
Alternative mammalian strategies leading towards gastrulation: losing polar trophoblast (Rauber's layer) or gaining an epiblast cavity DOI Creative Commons
Peter Pfeffer

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2022, Номер 377(1865)

Опубликована: Окт. 17, 2022

Using embryological data from 14 mammalian orders, the hypothesis is presented that in placental mammals, epiblast cavitation and polar trophoblast loss are alternative developmental solutions to shield central extraembryonic signalling. It argued such reciprocal signalling between edge of adjoining or mural with amniotic ectoderm necessary for induction gastrulation. This article part theme issue 'Extraembryonic tissues: exploring concepts, definitions functions across animal kingdom'.

Язык: Английский

Процитировано

18
Nodal signaling establishes a competency window for stochastic cell fate switching DOI Creative Commons
Andrew D. Economou, Luca Guglielmi, Philip East

и другие.

Developmental Cell, Год журнала: 2022, Номер 57(23), С. 2604 - 2622.e5

Опубликована: Дек. 1, 2022

Specification of the germ layers by Nodal signaling has long been regarded as an archetype how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset cells at early zebrafish embryo margin adopt endodermal fate, whereas their immediate neighbours, experiencing similar environment, become mesoderm. Combining pharmacology, quantitative imaging and single transcriptomics, we demonstrate that sustained establishes bipotential progenitor state from which can switch to fate or differentiate into Switching is random event, likelihood modulated Fgf signaling. This inherently imprecise mechanism nevertheless leads robust endoderm formation because buffering later stages. Thus, in contrast previous models morphogen action, temporal window when are competent undergo stochastic switch, rather than determining itself.

Язык: Английский

Процитировано

18
pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells DOI Creative Commons
Payam E. Farahani, Xiaoyu Yang, Emily V. Mesev

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Май 19, 2023

Receptor tyrosine kinases (RTKs) are major signaling hubs in metazoans, playing crucial roles cell proliferation, migration, and differentiation. However, few tools available to measure the activity of a specific RTK individual living cells. Here, we present pYtags, modular approach for monitoring user-defined by live-cell microscopy. pYtags consist an modified with activation motif that, when phosphorylated, recruits fluorescently labeled tandem SH2 domain high specificity. We show that enable on seconds-to-minutes time scales across subcellular multicellular length scales. Using pYtag biosensor epidermal growth factor receptor (EGFR), quantitatively characterize how dynamics vary identity dose activating ligand. orthogonal can be used monitor EGFR ErbB2 same cell, revealing distinct phases each RTK. The specificity modularity open door robust biosensors multiple may engineering synthetic receptors response programs.

Язык: Английский

Процитировано

10
The MEK-ERK signaling pathway promotes maintenance of cardiac chamber identity DOI Creative Commons
Yao Yao,

Deepam Gupta,

Deborah Yelon

и другие.

Development, Год журнала: 2024, Номер 151(4)

Опубликована: Янв. 31, 2024

ABSTRACT Ventricular and atrial cardiac chambers have unique structural contractile characteristics that underlie their distinct functions. The maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Previous studies zebrafish shown sustained FGF signaling acts upstream Nkx factors to maintain ventricular identity, but the rest this pathway remains unclear. Here, we show MEK1/2-ERK1/2 downstream promote maintenance. Inhibition MEK signaling, like inhibition results ectopic gene expression reduced both influence over a similar timeframe, when phosphorylated ERK (pERK) is present myocardium. However, role FGF-MEK activity appears be context-dependent: some regions are more sensitive than others signaling. Additionally, atrium, although endogenous pERK does not induce traits, heightened can provoke expression. Together, our data reveal roles MEK-ERK identities.

Язык: Английский

Процитировано

4