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

New developments in the biology of fibroblast growth factors DOI
David M. Ornitz,

Nobuyuki Itoh

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
Time-integrated BMP signaling determines fate in a stem cell model for early human development DOI Creative Commons
Seth Teague, Gillian Primavera, Bohan Chen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 17, 2024

Abstract How paracrine signals are interpreted to yield multiple cell fate decisions in a dynamic context during human development vivo and vitro remains poorly understood. Here we report an automated tracking method follow signaling histories linked large numbers of pluripotent stem cells (hPSCs). Using unbiased statistical approach, discover that measured BMP history correlates strongly with individual cells. We find response hPSCs varies more the duration than level. However, both level activity control choices only by changing time integral. Therefore, interchangeable this context. In model for patterning embryo, show predict pattern integral correctly predicts changes domains when is perturbed. Our data suggest mechanistically, integrated SOX2.

Язык: Английский

Процитировано

21
Selective utilization of glucose metabolism guides mammalian gastrulation DOI Creative Commons
Dominica Cao, Jenna Bergmann, Liangwen Zhong

и другие.

Nature, Год журнала: 2024, Номер 634(8035), С. 919 - 928

Опубликована: Окт. 16, 2024

The prevailing dogma for morphological patterning in developing organisms argues that the combined inputs of transcription factor networks and signalling morphogens alone generate spatially temporally distinct expression patterns. However, metabolism has also emerged as a critical developmental regulator

Язык: Английский

Процитировано

14
Phased ERK responsiveness and developmental robustness regulate teleost skin morphogenesis DOI Creative Commons
Nitya Ramkumar, Christian Richardson,

Makinnon O’Brien

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(10)

Опубликована: Март 5, 2025

Elongation of the vertebrate embryonic axis necessitates rapid expansion epidermis to accommodate growth underlying tissues. Here, we generated a toolkit visualize and quantify signaling in entire cell populations periderm, outermost layer epidermis, live developing zebrafish. We find that oriented divisions facilitate early periderm during axial elongation rather than addition from basal layer. Activity levels Extracellular signal-regulated kinase (ERK), downstream effector MAPK pathway, gauged by biosensor, predict cycle entry, optogenetic ERK activation regulates cycling dynamics. As development proceeds, rates peridermal proliferation decrease, activity becomes more pulsatile functionally transitions promote hypertrophic growth. Targeted genetic blockade division generates animals with oversized cells, yet, unexpectedly, adulthood is not impaired. Our findings reveal stage-dependent differential responsiveness marked developmental robustness growing teleost skin.

Язык: Английский

Процитировано

2
Self-organization of mouse embryonic stem cells into reproducible pre-gastrulation embryo models via CRISPRa programming DOI Creative Commons
Gerrald A. Lodewijk, Sayaka Kozuki,

Clara Han

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
NANOG initiates epiblast fate through the coordination of pluripotency genes expression DOI Creative Commons

Nicolas Allègre,

Sabine Chauveau,

Cynthia Dennis

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 21, 2022

Abstract The epiblast is the source of all mammalian embryonic tissues and pluripotent stem cells. It differentiates alongside primitive endoderm in a “salt pepper” pattern from inner cell mass (ICM) progenitors during preimplantation stages through activity NANOG, GATA6 FGF pathway. When how lineage specification initiated still unclear. Here, we show that coordinated expression pluripotency markers defines identity. Conversely, ICM progenitor cells display random cell-to-cell variability various markers, remarkably dissimilar signature independently activities. Coordination fails Nanog Gata6 double KO ( DKO ) embryos. Collectively, our data suggest NANOG triggers by ensuring subset cells, implying stochastic mechanism. These features are likely conserved, as suggested analysis human

Язык: Английский

Процитировано

35
RNA polymerase II pausing in development: orchestrating transcription DOI Creative Commons
Abderhman Abuhashem, Vidur Garg, Anna‐Katerina Hadjantonakis

и другие.

Open Biology, Год журнала: 2022, Номер 12(1)

Опубликована: Янв. 1, 2022

The coordinated regulation of transcriptional networks underpins cellular identity and developmental progression. RNA polymerase II promoter-proximal pausing (Pol pausing) is a prevalent mechanism by which cells can control synchronize transcription. Pol regulates the productive elongation step transcription at key genes downstream variety signalling pathways, such as FGF Nodal. Recent advances in our understanding machinery its role call for an assessment these findings within context development. In this review, we discuss current molecular basis function during organismal By critically assessing tools used to study process conclude that combining recently developed genomics approaches with refined perturbation systems has potential expand mechanistically functionally development beyond.

Язык: Английский

Процитировано

30
A guide to ERK dynamics, part 2: downstream decoding DOI Creative Commons
Abhineet Ram,

Devan Murphy,

Nicholaus DeCuzzi

и другие.

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
An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development DOI Creative Commons
Scott G. Wilcockson, Luca Guglielmi,

Pablo Araguas Rodriguez

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(23), С. 2802 - 2818.e5

Опубликована: Сен. 15, 2023

Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role Erk vivo, as gradient activated diphosphorylated (P-Erk) induced by fibroblast growth factor (Fgf) at blastula margin. Here, we describe improved Erk-specific biosensor, which term modified translocation reporter (modErk-KTR). We demonstrate utility this biosensor vitro and developing Drosophila embryos. Moreover, show that Fgf/Erk dynamic coupled tissue during both development. activity rapidly extinguished just prior mitosis, refer mitotic erasure, inducing periods inactivity, thus providing source heterogeneity asynchronously dividing tissue. Our transgenic lines represent important resource for interrogating vivo.

Язык: Английский

Процитировано

18
Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst DOI Creative Commons
Claire Simon,

Afshan McCarthy,

Laura Woods

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 4, 2024

Abstract Studies in the mouse demonstrate importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) specification embryo-fated epiblast yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) prior to implantation. Molecular mechanisms regulating early lineages human development are comparatively unclear. Here we show that exogenous FGF stimulation leads expanded molecular marker expression, at expense epiblast. Conversely, specifically inhibiting ERK activity expansion functionally capable giving rise naïve pluripotent stem cells. Single-cell transcriptomic analysis indicates these downregulate signalling upregulate markers associated with pluripotency. Our functional study demonstrates for first time governing ICM development, whereby segregation occurs during maturation mammalian embryo an signal-dependent manner.

Язык: Английский

Процитировано

7