Acute dietary methionine restriction highlights sensitivity of neocortex development to metabolic variations DOI Creative Commons
Sulov Saha,

Clémence Debacq,

Christophe Audouard

и другие.

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

Опубликована: Сен. 10, 2024

ABSTRACT Methionine -an essential amino acid that has to be provided by nutrition- and its metabolite S-Adenosyl methionine (SAM) are indispensable for cell proliferation, stem maintenance epigenetic regulation 1–5 , three processes central embryonic development 6 . Previous studies using chronic dietary restriction of methyl donors prior during gestation indicated (MR) is detrimental the or growth neocortex 7,8 however, consequences acute MR have not been extensively studied. Here, we designed a regime coinciding with neurogenic phases in mouse. Our results indicate 5 days leads severe reduction neuronal production. In comparison, liver heart was unaffected, highlighting an organ-specific response which also observed at cellular molecular levels. Progenitor cohort labeling revealed time-dependent sensitivity cycle analyses after MR, progenitors stalled S/G2 phases. Unexpectedly, induced completely rescued birth when switching dam back control diet remaining gestation, uncovering mechanism catch-up growth. Using multiplexed imaging probed metabolic markers following show pyruvate metabolism rewired progenitors. Altogether, our data uncover transient state quiescence G2/S metabolically distinct from G0 associated efficient More globally, study highlights both extreme developing changes remarkable plasticity.

Язык: Английский

HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis DOI Creative Commons
Li Luo, Jung‐Hyun Kim, Iliana Herrera

и другие.

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(3)

Опубликована: Фев. 2, 2025

Mutated tumor cells undergo changes in chromatin accessibility and gene expression, resulting aberrant proliferation differentiation, although how this occurs is unclear. HMGA1 regulators are abundant stem oncogenic diverse tissues; however, their role colon tumorigenesis only beginning to emerge. Here, we uncover a previously unknown epigenetic program whereby amplifies Wnt signaling during driven by inflammatory microbiota and/or Adenomatous polyposis coli (Apc) inactivation. Mechanistically, "opens" upregulate the cell regulator, Ascl2, downstream effectors, promoting Paneth-like states while depleting differentiated enterocytes. Loss of just one Hmga1 allele within epithelium restrains mutant Apc microbiota. However, deficiency has minimal effects under homeostatic conditions. In human cancer cells, directly induces ASCL2 recruiting activating histone marks. Silencing disrupts properties, whereas reexpression partially rescues these phenotypes. Further, coexpressed upregulated colorectal cancer. Together, our results establish as an gatekeeper signals state conditions APC inactivation, illuminating potential therapeutic target

Язык: Английский

Процитировано

2
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

10
Metabolic mechanisms of species-specific developmental tempo DOI Creative Commons
Ryohei Iwata, Pierre Vanderhaeghen

Developmental Cell, Год журнала: 2024, Номер 59(13), С. 1628 - 1639

Опубликована: Июнь 20, 2024

Development consists of a highly ordered suite steps and transitions, like choreography. Although these sequences are often evolutionarily conserved, they can display species variations in duration speed, thereby modifying final organ size or function. Despite their evolutionary significance, the mechanisms underlying species-specific scaling developmental tempo have remained unclear. Here, we will review recent findings that implicate global cellular mechanisms, particularly intermediary protein metabolism, as modifiers tempo. In various systems, from somitic cell oscillations to neuronal development, metabolic pathways differences. These been linked mitochondrial which influence speed transitions. Thus, regulate together with other processes, including proteostasis chromatin remodeling. By linking metabolism evolution trajectories, provide opportunities decipher how timing organism fitness.

Язык: Английский

Процитировано

9
Metabolism-driven chromatin dynamics: Molecular principles and technological advances DOI
Varun Sahu, Chao Lü

Molecular Cell, Год журнала: 2025, Номер 85(2), С. 262 - 275

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma DOI Open Access
Katrina I. Paras, Julia Brunner, Jacob A. Boyer

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

Abstract PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here we show PAX3-FOXO1 + RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in de novo synthesis, including dihydrofolate reductase (DHFR). Consequently, display sensitivity to inhibition DHFR the chemotherapeutic drug methotrexate, this is rescued provision nucleotides. Methotrexate treatment mimics metabolic transcriptional impact silencing, reducing genes related PAX3-FOXO1-driven Accordingly, methotrexate slows growth multiple tumor xenograft models, but not fusion-negative counterparts. Taken together, these data demonstrate induces states characterized nominate as addition current therapeutic arsenal for pediatric tumors.

Язык: Английский

Процитировано

0
Oncogenic competence: balancing mutations, cellular state, and microenvironment DOI
Lisa Pavinato, Arianna Baggiolini

Trends in cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Cell–cell heterogeneity in phosphoenolpyruvate carboxylase biases early cell fate priming in Dictyostelium discoideum DOI Creative Commons
Kenichi Abe,

Hidenori Hashimura,

Haruka Hiraoka

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Фев. 4, 2025

Glucose metabolism is a key factor characterizing the cellular state during multicellular development. In metazoans, metabolic of undifferentiated cells correlates with growth/differentiation transition and cell fate determination. Notably, Amoebozoa species Dictyostelium discoideum biased by presence glucose also correlated early differences in intracellular ATP. However, relationship between cell–cell heterogeneity, differentiation, unclear. To address link differentiation D. , we studied role phosphoenolpyruvate carboxylase (PEPC), enzyme PEP-oxaloacetate-pyruvate node, core junction that dictates flux glycolysis, TCA cycle, gluconeogenesis. We demonstrate there heterogeneity PEPC promoter activity vegetative cells, which depends on nutrient conditions, high differentiate into spores. The null mutant exhibited an aberrantly prestalk/prespore ratio, spore mass fruiting body was glassy consisted immature Furthermore, had ATP levels low mitochondrial membrane potential. Our results suggest importance enzymes priming.

Язык: Английский

Процитировано

0
Pyruvate kinase M2 modulates mitochondrial dynamics and EMT in alveolar epithelial cells during sepsis-associated pulmonary fibrosis DOI Creative Commons

Jinhua Feng,

Xi Huang, Yawen Peng

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 19, 2025

Язык: Английский

Процитировано

0
Mitochondrial substrate oxidation regulates distinct cell differentiation outcomes DOI
Woo Yong Park,

Claudia Montufar,

Elma Zaganjor

и другие.

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Development of Iron Oxide Nanochains as a Sensitive Magnetic Particle Imaging Tracer for Cancer Detection DOI Creative Commons
P. P. Praveen Kumar,

Md Nafiujjaman,

Ashley V. Makela

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

The advancement of imaging technologies plays a crucial role in improving the diagnosis and monitoring diseases, including cancer. This study introduces new design iron oxide-based nanoparticles specifically developed for magnetic particle (MPI), aimed at tracking diagnosing breast cancer more effectively. By precisely controlling size, shape, properties these nanoparticles, we enhance responsiveness MPI, resulting an increased signal. In our research, established novel synthetic route fabricating oxide nanochains (FeONCs) characterized by their uniform shape which contribute to high suitable MPI applications. Initial results indicate FeONCs exhibit superior compared conventional spherical superparamagnetic nanocubes, reported nanoworm-type structures. Magnetic relaxometry studies revealed that provide higher sensitivity than commonly used VivoTrax Synomag D50 D70 MPI. Further, size significantly influence cellular uptake. vivo experiments using orthotopic mouse models allow us assess biocompatibility characteristics confirming efficacy. Furthermore, conjugating with RGD peptide, ability target cancer, establishing them as promising tracers applications sensitivity. Thus, findings highlight improve quality, facilitating early detection accurate paves way innovative diagnostic strategies personalized treatment options. Future research will focus on fine-tuning surface chemistry further targeting efficiency optimization practice clinical applications, particularly MPI-based hyperthermia therapy.

Язык: Английский

Процитировано

0