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Results for “cell states”

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At least 19 recordsLinked to original sources
PubMed1991

Effects of transforming growth factor-beta 1 on growth of aortic smooth muscle cells. Influences of interaction with growth factors, cell state, cell phenotype, and cell cycle.

Transforming growth factor (TGF)-beta 1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta 1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta 1 at 10-10,000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC-derived growth factor, or fetal bovine serum (FBS). TGF-beta 1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta 1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta 1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition.

Animals↗
PubMed2026

A latent activated olfactory stem cell state revealed by single-cell transcriptomic and epigenomic profiling.

The olfactory epithelium is one of the few regions of the nervous system that sustains neurogenesis throughout life. Its experimental accessibility makes it especially tractable for studying molecular mechanisms that drive neural regeneration in response to injury. In this study, we used single-cell sequencing to identify transcriptional and epigenetic processes involved in determining olfactory epithelial stem cell fate during injury-induced regeneration. By combining gene expression and accessible chromatin profiles of individual lineage-traced olfactory stem cells, we identified transcriptional heterogeneity among activated stem cells at a stage when cell fates are being specified. We further identified a subset of resting cells that appears poised for activation, characterized by accessible chromatin around silent genes prior to their expression in response to injury. These results provide evidence for a latent activated stem cell state in which a subset of quiescent olfactory epithelial stem cells are epigenetically primed to support injury-induced regeneration.

Animals↗
PubMed1987

The cytoskeletal mechanics of brain morphogenesis. Cell state splitters cause primary neural induction.

There is a functional device in embryonic ectodermal cells that we propose causes them to differentiate into either neuroepithelial or epidermal tissue during the process called primary neural induction. We call this apparatus the "cell state splitter." Its main components are the apical microfilament ring and the coplanar apical mat of microtubules, which exert forces in opposite radial directions. We analyze the mechanical interaction between these cytoskeletal components and show that they are in an unstable mechanical equilibrium. The role of the cell state splitter is thus to create a mechanical instability corresponding to the embryonic state of "competence" in an otherwise mechanically stable cell. When the equilibrium of the cell state splitter is disturbed so as to produce a slight contraction of the apical end, apical contraction continues and the distinctive columnar neuroepithelial cells are produced. A slight expansion from the equilibrium state, on the other hand, results in flattened epidermal cells. The calculated forces are consistent with the known constitutive and force-generating properties and morphology of microfilaments and microtubules, and with free tubulin concentrations. There are no free parameters in the analysis. The first cells to assume the neuroepithelial state lie over the notochord. Propagation of the neuroepithelial state (homoiogenetic induction) then proceeds via stretch-induced constriction of the apical microfilament rings, until a hemisphere is covered, at which point the high rate of change of the meridional stress component necessary for further propagation vanishes. The remaining cells are stretched somewhat by this process and become epidermis. A sharp boundary between the tissues is thus formed (explaining "compartmentalization" and the binary nature of differentiation in general). Normal induction apparently involves setup of the cell state splitters in all of the ectoderm cells, perhaps synchronously timed by global embryo tension. The initial transition of cells from the ectodermal to the neuroepithelial state begins at the notoplate, where cell attachments to the notochord may both cause basal actin deposition and significantly reduce the stress induced in the ectoderm by the global tension, biasing the notoplate cell state splitters toward the neuroepithelial state. Introduction of an organizer or other solid substrate (artificial inducer) elsewhere, to which ectodermal cells can adhere, may likewise have both of these effects. Differentiation to either epidermis or neuroepithelium is thus a mechanical event followed by the synthesis of specific proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Cell lineage and cell states in the Drosophila embryo.

Much of this essay is a cautionary tale about the inherent difficulty of building theories to explain pattern formation in embryos. In particular, I discuss the relationship between cell state and cell lineage. The idea that embryonic cells can occupy discrete genetic states is an old one but, because of the mass of new information from Drosophila developmental genetics, it has been given new life. I propose an operational definition of a cell state and argue that a true cell state should be propagated faithfully through cell lineage for at least some divisions. The genes involved should have a controlling role and the borders between populations of cells in two different states should be so sharp that cells fall clearly into one state or another.

Animals↗
PubMed2026

Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.

Cancer arises from genetic and epigenetic alterations that reshape chromatin, transcriptional regulation, and malignant cell states. To chart cancer-intrinsic regulatory programs, we build a pan-cancer single-cell atlas of 60 cancer cell lines spanning 16 tissue origins and 20 cancer types, comprising 240,957 snRNA-seq and 223,347 snATAC-seq profiles. Integrative analyses reveal cell-state heterogeneity, core gene-regulatory networks, and a conserved EMT axis transcending tissue of origin; copy-number analysis identifies transcription factor amplification and hyperactivation as drivers of state reprogramming. Comparing cutaneous melanoma with acral melanoma, a rare subtype underrepresented in previous studies, uncovers a universal inflammation-suppressive program in acral and an inflamed landscape in cutaneous melanoma, with JAK-STAT activity as the central discriminator. Integrating data across models and patient cohorts links tumor-intrinsic regulation to microenvironmental composition and therapeutic response. By profiling rare alongside common subtypes, this atlas offers a resource for mapping pan-cancer and subtype-specific regulatory programs shaping cell-state plasticity.

Humans↗
PubMed2026

Genome-wide chromatin recording resolves dynamic cell state changes.

Understanding how the chromatin state of a cell influences its future behavior is a major challenge throughout biology. However, most chromatin profiling methods are limited to endpoint assays. Here, we present LagTag, a method for recovery of earlier and endpoint chromatin states in the same mammalian cells. In this approach, transient activity of bacterial adenine methyltransferase fusions records the DNA-binding profiles of chromatin-associated proteins of interest at earlier time points. Subsequent tagmentation and sequencing recover the earlier chromatin profile from adenine methylation profiles, alongside endpoint profiles of endogenous chromatin-associated proteins. We verified that LagTag profiles aligned with those from established methods in mouse and human cells. We then applied LagTag to record and recover dynamic chromatin state transitions during mouse embryonic stem cell differentiation, capturing transcriptional signatures from pre- and post-differentiation time points within the same cell population. LagTag thus provides a foundation for temporally resolved chromatin profiling. A record of this paper's transparent peer review process is included in the supplemental information.

chromatin organization↗
PubMed2026

Genome-wide chromatin recording resolves dynamic cell state changes.

Understanding how the chromatin state of a cell influences its future behavior is a major challenge throughout biology. However, most chromatin profiling methods are limited to endpoint assays. Here, we present LagTag, a method for recovery of earlier and endpoint chromatin states in the same mammalian cells. In this approach, transient expression of bacterial adenine methyltransferase fusions records the DNA binding profiles of chromatin-associated proteins of interest at earlier timepoints. Subsequent tagmentation and sequencing recovers the earlier chromatin profile from adenine methylation profiles, alongside endpoint profiles of endogenous chromatin-associated proteins. We verified that LagTag profiles aligned with those from established methods in mouse and human cells. We then applied LagTag to record and recover dynamic chromatin state transitions during mouse embryonic stem cell differentiation, capturing transcriptional signatures from pre- and post-differentiation timepoints within the same cell population. LagTag thus provides a foundation for temporally resolved chromatin profiling.

Journal Article↗
PubMed2026

Multimodal atlas of human atherosclerosis links granular vascular cell states to coronary artery disease risk.

Advances in single-cell and spatial assays have revolutionized the scale and resolution of molecular tissue profiling. Here we present MetaPlaq, a multimodal atlas of human atherosclerotic arterial beds comprising over a million cells across single-cell transcriptomics, epigenomics and high-resolution spatial expression assays. We map granular cell states and disease-relevant transcriptional programs within the native tissue context of coronary arteries. Furthermore, we map cardiovascular GWAS signals to smooth muscle cells (SMCs) and endothelial cells (ECs) and uncover the cis-regulatory architecture governing their phenotypic transitions. Our comprehensive epigenomic reference allowed us to build cell-specific enhancer-gene link maps and multimodal gene regulatory networks (GRNs) underlying disease-relevant states such as osteogenic SMCs and ECs undergoing mesenchymal transition. We also integrate SMC and EC disease-associated gene sets with GRNs to nominate key transcription factors such as PRRX1, BNC2 and ELK3 regulating atherosclerosis-relevant transcriptional programs. Finally, we layer single-cell and spatial modalities to fine-map GWAS variants with improved cell and anatomical context. We highlight candidate cell-specific regulatory mechanisms at less characterized CAD loci, including FGD5 and MCF2L in ECs. Together, this atlas represents an important step towards fully interpreting genetic risk loci and informing new therapeutic strategies for cardiovascular disease.

Journal Article↗
PubMed2026

PLK1/FOXM1-associated tumor-cell state and macrophage-related immune features in endometrial cancer.

BACKGROUND: Polo-like kinase 1 (PLK1) and forkhead box M1 (FOXM1) have been widely studied in various cancers; however, their expression characteristics in endometrial cancer (EC) and their potential association with tumor microenvironment remodeling remain insufficiently characterized. METHODS: This study integrated The Cancer Genome Atlas uterine corpus endometrial carcinoma cohort, Gene Expression Omnibus, pan-cancer transcriptomic data, Human Protein Atlas/Clinical Proteomic Tumor Analysis Consortium, and local immunohistochemistry data to evaluate PLK1 expression and clinicopathological relevance across transcriptomic, proteomic, and histopathological data. Differential expression, survival, gene-set enrichment, transcription-factor enrichment, and immune-infiltration analyses characterized PLK1-associated features. In vitro experiments combined EC cell lines AN3CA and HEC-1A with co-immunoprecipitation, Western blotting, Transwell assays, and a THP-1 conditioned-medium model. Drug-response prediction and structure-based analysis prioritized candidate therapeutic hypotheses. RESULTS: PLK1 was consistently upregulated at both mRNA and protein levels in EC and was associated with higher tumor grade and International Federation of Gynecology and Obstetrics (FIGO) stage. In survival analysis, higher PLK1 expression was associated with poorer overall survival in univariable models but not after adjustment for age, tumor grade, and FIGO stage. Functional enrichment analysis showed that PLK1-associated genes were mainly involved in cell-cycle and mitotic processes. FOXM1 was identified as a potential candidate component of the PLK1-associated transcriptional program and was positively correlated with PLK1 expression and cell-cycle-related features. In vitro experiments supported an interaction between PLK1 and FOXM1 and suggested that FOXM1 Thr600 phosphorylation-related alterations were associated with migration and invasion phenotypes. Furthermore, the PLK1/FOXM1-associated tumor-cell state was linked to macrophage-related immune features and changes in the M2-like marker profile of THP-1-derived macrophage-like cells. Drug response analyses suggested differential predicted sensitivity patterns in PLK1-high tumors, providing candidate therapeutic hypotheses for further validation. CONCLUSION: The PLK1/FOXM1-associated tumor-cell state may represent a distinct molecular feature associated with proliferative activity, invasive phenotypes, and macrophage-related immune features in EC. This study provides preliminary evidence supporting the biological relevance of this molecular feature and highlights potential therapeutic directions for future investigation.

FoxM1↗
PubMed1992

Identification of a transitional cell state in the developmental pathway to carrot somatic embryogenesis.

We have located a novel carbohydrate epitope in the cell walls of certain single cells in embryogenic, but not in non-embryogenic, suspension cultures of carrot. Expression of this epitope, recognized by the mAb JIM8, is regulated during initiation, proliferation, and prolonged growth of suspension cultures such that changes in the abundance of JIM8-reactive cells always precede equivalent changes in embryogenic potential. Therefore, a direct correlation exists between the presence of the JIM8-reactive cell wall epitope and somatic embryo formation. The JIM8-reactive cell wall epitope is expressed in the cell walls of three types of single cells and one type of cell cluster. One of the single cell types seems able to follow one of two phytohormone-controlled developmental pathways, either a cell elongation pathway that eventually leads to cell death, or a cell division pathway that gives rise to proembryogenic masses. We demonstrate that all JIM8-reactive cell types in embryogenic carrot suspension cultures are developmentally related, and that the switch by one of them to somatic embryogenesis is accompanied by the immediate dissipation of the JIM8-reactive cell wall epitope. The cell wall carbohydrate epitope recognized by JIM8 therefore represents a cell wall marker for a very early transitional cell state in the developmental pathway to carrot somatic embryogenesis.

Antibodies, Monoclonal↗
PubMed2025

Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial cell state.

Epithelial cancers disrupt tissue architecture and are often driven by mutations in genes that play important roles in normal epithelial morphogenesis. The intrahepatic biliary system is an epithelial tubular network that forms within the developing liver via the de novo initiation and expansion of apical lumens. Intrahepatic biliary tumors (intrahepatic cholangiocarcinoma) commonly harbor activating genomic alterations in the FGFR2 receptor tyrosine kinase, which plays important roles in epithelial morphogenesis in other developmental settings. Using a physiologic and quantitative 3D model we demonstrate that FGFR signaling is important for biliary morphogenesis and that oncogenic FGFR2 fusions and in-frame deletions disrupt biliary architecture. Importantly, we show that the trafficking of and signaling from the FGFR2 mutants, as well as their phenotypic impacts, are governed by the epithelial state of the cell. Unexpectedly, we also found that distinct tumor-driving FGFR2 mutants disrupt biliary morphogenesis in completely different and clinically relevant ways, informing our understanding of morphogenesis and tumorigenesis and highlighting the importance of convergent studies of both.

Journal Article↗
PubMed1985

Histone H1(0): a maintainer of the differentiated cell state?

Functional and structural effects of histones H1 and H1(0) were studied on isolated chromatin and nuclei from embryonic skeletal muscle as well as on cultured cells. The results showed that: H1 was responsible for a greater compaction of chromatin than H1(0) as evidenced by sedimentation. In contrast, H1(0) inhibited DNA synthesis in chromatin and cells to a greater extent than H1. No significant difference between the two histones on RNA synthesis inhibition was observed. histones H1 and H1(0) evidenced a quantitative increase in developing muscle cells. The results indicate that H1(0) may not be the inducer of the differentiated cell state, but rather assists in the maintenance of that state.

Animals↗
PubMed1987

Predicted steady-state cell size distributions for various growth models.

The question of how an individual bacterial cell grows during its life cycle remains controversial. In 1962 Collins and Richmond derived a very general expression relating the size distributions of newborn, dividing and extant cells in steady-state growth and their growth rate; it represents the most powerful framework currently available for the analysis of bacterial growth kinetics. The Collins-Richmond equation is in effect a statement of the conservation of cell numbers for populations in steady-state exponential growth. It has usually been used to calculate the growth rate from a measured cell size distribution under various assumptions regarding the dividing and newborn cell distributions, but can also be applied in reverse--to compute the theoretical cell size distribution from a specified growth law. This has the advantage that it is not limited to models in which growth rate is a deterministic function of cell size, such as in simple exponential or linear growth, but permits evaluation of far more sophisticated hypotheses. Here we employed this reverse approach to obtain theoretical cell size distributions for two exponential and six linear growth models. The former differ as to whether there exists in each cell a minimal size that does not contribute to growth, the latter as to when the presumptive doubling of the growth rate takes place: in the linear age models, it is taken to occur at a particular cell age, at a fixed time prior to division, or at division itself; in the linear size models, the growth rate is considered to double with a constant probability from cell birth, with a constant probability but only after the cell has reached a minimal size, or after the minimal size has been attained but with a probability that increases linearly with cell size. Each model contains a small number of adjustable parameters but no assumptions other than that all cells obey the same growth law. In the present article, the various growth laws are described and rigorous mathematical expressions developed to predict the size distribution of extant cells in steady-state exponential growth; in the following paper, these predictions are tested against high-quality experimental data.

Bacteria↗
PubMed1988

An inwardly-directed sodium-amino acid cotransporter influences steady-state cell volume in slices of rat renal papilla incubated in hyperosmotic media.

The effect of a neutral amino acid, 2-aminoisobutyric acid (AIB) on steady state cell volume has been examined in rat renal papillary slices incubated in hyperosmotic media (2,000 mosmol/kg H2O) containing high concentrations of NaCl and urea (thus imitating papillary interstitial fluid in the intact kidney during antidiuresis). Volumes were significantly increased (P less than 0.001) when external AIB was raised from 0.1 to 10 mmol/l. Na+-dependent AIB uptake occurred, and there were net increases in cell contents of Na+ and Cl-. Replacement of Na+ by Li+, but not by other cations, did not influence the effect of AIB concentration on cell volume, but this was abolished when Cl- was replaced by other anions. The effect of AIB was abolished by diphenylamine-2-carboxylate (10(-3) mmol/l), bumetanide (at 1 mmol/l but not 10(-2) mmol/l) and by N,N'-dicyclohexylcarbodiimide (0.5 mmol/l), but not by amiloride (1 mmol/l) or 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid (1 mmol/l), and was enhanced by the presence of Ba2+ or quinine (1 mmol/l). The findings are interpreted in terms of an inwardly-directed Na+-amino acid cotransporter, which determines steady-state volume, requires simultaneous entry of Cl- through conductive pathways, and whose effects on cell volume are moderated by K+ efflux through volume-sensitive K+ channels.

Amino Acids↗
PubMed1972

Anaesthesia in sickle-cell states: a plea for simplicity.

505 patients with various haemoglobinopathies were given a general anaesthetic between January 1970 and February 1972. One patient with haemoglobin SC disease and one patient with sickle-cell trait (HbAS) died postoperatively. Four other patients who were sickling positive, but whose genotypes were unknown, died, one from sickle-cell crisis precipitated by haemorrhage.A simple anaesthetic technique together with good postoperative care can provide safe general anaesthesia for patients with sickle-cell states. A plea is made for simplicity in the anaesthetic management of these patients.

Adult↗
PubMed1977

High-density induction of a quiescent cell state in Physarum polycephalum.

The non-histone protein complement of Physarum polycephalum changes rapidly when microplasmodia are subjected to conditions of high density. The changes in these proteins induced by high density are similar to the changes observed during starvation-induced encystment. A 50% decrease in DNA synthesis, observed after 7 h of starvation, is observed after only 1 h of high density. High density also results in a decrease in RNA synthesis comparable to decreases induced by prolonged starvation. Total heterochromatin increases in response to either high density or starvation. Increased heterochromatization is preceded by an increase in nuclear actin. Mitochondrial morphology and cytoplasmic organization are also similarly altered by starvation and high density. These observations suggest the possibility of a generalized mechanism for cellular transition from active growth to a non-proliferative cell state.

Cell Differentiation↗
PubMed1988

Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo.

Segment polarity genes are expressed and required in restricted domains within each metameric unit of the Drosophila embryo. We have used the expression of two segment polarity genes engrailed (en) and wingless (wg) to monitor the effects of segment polarity mutants on the basic metameric pattern. Absence of patched (ptc) or naked (nkd) functions triggers a novel sequence of en and wg patterns. In addition, although wg and en are not expressed on the same cells absence of either one has effects on the expression of the other. These observations, together with an analysis of mutant phenotypes during development, lead us to suggest that positional information is encoded in cell states defined and maintained by the activity of segment polarity gene products.

Animals↗