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Results for “cell state transition”

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At least 19 recordsLinked to original sources
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↗
PubMed2026

Identifying fate-determining transcription factors with single-cell omics.

Single-cell sequencing enables the systematic discovery of cell fate-determining transcription factors (TFs), or key TFs, that define cellular identity or drive cell state transitions. A wide range of computational methods have been developed for this goal, but they differ substantially in the input data and the biological questions they address. In this article, we systematically review computational approaches for key TF identification and organize them from three perspectives: whether they identify TFs defining cell state identity or driving state transitions, whether transitions are modeled as discrete or continuous processes, and whether TFs act individually or combinatorially. We summarize key features and application scenarios of relevant methods to guide tool selection and discuss emerging trends in this field toward programmable and active control of cell fate.

Transcription Factors↗
PubMed2025

Trajectory inference from single-cell genomics data with a process time model.

Single-cell transcriptomics experiments provide gene expression snapshots of heterogeneous cell populations across cell states. These snapshots have been used to infer trajectories and dynamic information even without intensive, time-series data by ordering cells according to gene expression similarity. However, while single-cell snapshots sometimes offer valuable insights into dynamic processes, current methods for ordering cells are limited by descriptive notions of "pseudotime" that lack intrinsic physical meaning. Instead of pseudotime, we propose inference of "process time" via a principled modeling approach to formulating trajectories and inferring latent variables corresponding to timing of cells subject to a biophysical process. Our implementation of this approach, called Chronocell, provides a biophysical formulation of trajectories built on cell state transitions. The Chronocell model is identifiable, making parameter inference meaningful. Furthermore, Chronocell can interpolate between trajectory inference, when cell states lie on a continuum, and clustering, when cells cluster into discrete states. By using a variety of datasets ranging from cluster-like to continuous, we show that Chronocell enables us to assess the suitability of datasets and reveals distinct cellular distributions along process time that are consistent with biological process times. We also compare our parameter estimates of degradation rates to those derived from metabolic labeling datasets, thereby showcasing the biophysical utility of Chronocell. Nevertheless, based on performance characterization on simulations, we find that process time inference can be challenging, highlighting the importance of dataset quality and careful model assessment.

Single-Cell Analysis↗
PubMed2025

Deciphering Cell Fate and Clonal Dynamics via Integrative Single-Cell Lineage Modeling.

Through natural or synthetic lineage barcodes, single-cell technologies now enable the joint measurement of molecular states and clonal identities, providing an unprecedented opportunity to study cell fate and dynamics. Yet, most computational methods for inferring cell development and differentiation rely exclusively on transcriptional similarity, overlooking the lineage information encoded by lineage barcodes. This limitation is exemplified by T cells, where subtle transcriptional differences mark divergent fates with distinct biological activity. Single-cell RNA and matched TCR sequencing is now ubiquitous in the analysis of clinical samples, where the TCR sequence provides an endogenous clonal barcode and could reveal clonal T cell responses. We present Clonotrace, a computational framework that jointly models gene expression and clonotype information to infer cell state transitions and fate biases with higher fidelity. While motivated by challenges in analyzing T cell populations, especially in the tumor microenvironment and immunotherapy settings, Clonotrace is broadly applicable to any lineage-barcoded single-cell dataset. Across diverse systems including T cells, hematopoietic differentiation, and cancer therapy resistance models, Clonotrace reveals differentiation hierarchies, distinguishes unipotent from multipotent states, and identifies candidate fate-determining genes driving lineage commitment.

Journal Article↗
PubMed2025

Deciphering Cell Fate and Clonal Dynamics via Integrative Single-Cell Lineage Modeling.

Through natural or synthetic lineage barcodes, single-cell technologies now enable the joint measurement of molecular states and clonal identities, providing an unprecedented opportunity to study cell fate and dynamics. Yet, most computational methods for inferring cell development and differentiation rely exclusively on transcriptional similarity, overlooking the lineage information encoded by lineage barcodes. This limitation is exemplified by T cells, where subtle transcriptional differences mark divergent fates with distinct biological activity. Single-cell RNA and matched TCR sequencing is now ubiquitous in the analysis of clinical samples, where the TCR sequence provides an endogenous clonal barcode and could reveal clonal T cell responses. We present Clonotrace, a computational framework that jointly models gene expression and clonotype information to infer cell state transitions and fate biases with higher fidelity. While motivated by challenges in analyzing T cell populations, especially in the tumor microenvironment and immunotherapy settings, Clonotrace is broadly applicable to any lineage-barcoded single-cell dataset. Across diverse systems including T cells, hematopoietic differentiation, and cancer therapy resistance models, Clonotrace reveals differentiation hierarchies, distinguishes unipotent from multipotent states, and identifies candidate fate-determining genes driving lineage commitment.

Journal Article↗
PubMed2026

Spatial proximity sequencing maps developmental dynamics in the germinal center.

Spatial profiling of proteins and protein interactions facilitates understanding of cell functions within tissues and is essential for studies in signaling, immunity, and cancer. We present spatial proximity sequencing (Sprox-seq) for simultaneous profiling of surface proteins, protein complexes, and mRNAs, recording the tissue location of each molecule. Sprox-seq profiled 32 proteins, 528 pairwise interactions, and thousands of mRNAs with spatial resolution across human tonsils and germinal centers. Mapping tissue-wide protein interactions recapitulated RNA-defined tissue architecture but also revealed higher interaction complexity in the light zone. Protein-interaction trajectories uncovered a B cell state transition distinct from that inferred by RNA. Integrated protein-complex and mRNA analysis related spatially enriched complexes with mitotic pathways. Sprox-seq captured cell-cell interactions, such as B cell-follicular dendritic cell interactions mediated by the receptor complex VLA-4-VCAM1. Sprox-seq provides a spatially resolved multi-modal view of cell states and an integrated study of protein and cellular interactions across tissues.

Humans↗
PubMed2025

Cell-type-specific defense priming and NHP-dependent systemic immunity against Pectobacterium in Chinese cabbage.

Defense priming is an effective strategy for mounting the defensive capacity of plants. Primed plants undergo minimal changes, enabling rapid, robust responses to subsequent pathogen attack. The cell-type-specific mechanisms underlying priming and systemic immunity remain unclear. Using single-nucleus RNA sequencing (snRNA-seq), we reveal how primed Chinese cabbage coordinates N-hydroxypipecolic acid (NHP)-dependent systemic immunity against Pectobacterium carotovorum. NHP accumulates as a phloem-mobile priming signal. snRNA-seq identified a priming-specific epidermal cell state transition and transcriptional cascade: BrWRKY18-1 activates BrWRKY33-1 expression during priming, initiating NHP-dependent systemic immunity. At post-challenge primed state, pathogenesis-related genes (PRs), such as BrPR3, BrPR4-1, and BrPR4-2, are predominantly expressed in systemic tissues to inhibit infection. Notably, the functionality of these PR genes in immunity necessitates their expression in all cells to effectively enhance defensive resistance. This NHP-transcription factor-PR axis couples mobile signaling to systemic immunity, elucidating cell-type-specific defense priming.

Plant Immunity↗
PubMed1977

Inhibition of ribonucleases by ribonucleotides and transition state analogs in cell-free extracts from Ehrlich ascites tumor cells.

We investigated the ribonucleolytic breakdown of poly(U), poly(A), RNA trascribed from calf thymus DNA with E. coli RNA polymerase, ribosomal RNA, tRNA and mengovirus RNA by an enzyme fraction obrained from a postribosomal supernatant of Ehrlich ascites tumor cells. The single-stranded homopolyribonucleotides are preferentially degraded by the enzyme fraction with the production of ribonucleoside 5'-monophosphates. The RNase activity is completely dependent on the presence of Mg2+ ions and is highest at Mg2+ and K+ concentrations optimal for cell-free protein synthesis. Ribonucleoside 5'-monophosphates, ribonucleoside 2'(3')-monophosphates, ribonucleoside 2'(3'),5'-bisphosphates and transition state analogs consisting of vanadyl sulfate and either ribonucleosides or ribonucleoside 5'-monophosphates in a molar ratio 1:1 inhibit the ribonucleolytic activity of the enzyme fraction. The ribonucleoside 2'(3'),5'-bisphosphates and the transition state analogs are the most effective inhibitors. However, only in the presence of ribonucleoside 2'(3'),5'-bisphosphates a concomitant stimulation by 50 to 60% of poly(U)-directed polyphenylalanine synthesis is observed; all the other RNase inhibitors tested also inhibit polypeptide synthesis. The results of preliminary experiments show that poly(U) and ribonucleoside 2'(3'),5'-bisphosphates are well suited as ligands for affinity chromatography of ribonucleases from Ehrlich ascites tumor cells.

Animals↗
PubMed1977

PH-dependent changes of 2,3-bisphosphoglycerate in human red cells during transitional and steady states in vitro.

A systematic study of the pH-dependent changes in the range 6.6--7.4 of 2,3-bisphosphoglycerate and the adenine nucleotides was performed in the presence and absence of glucose during transitional and steady states. 1. The results indicatethat 2,3-gisphosphoglycerate phosphatase breaks down 2,3-bisphosphoglycerate nearly independent of pH at a rate of 480 mumol 2,3-bisphosphoglycerate x1 cells-1xh-1.2,3-Bisphosphoglycerate mutase is practically completely inhibited below pH value increases in long-term experiments with lower 2,3-bisphosphoglycerate levels. The formation of pyruvate corresponds to the breakdown of 2,3-bisphosphoglycerate afterconsumption of an unknown reducing substance.

Adenosine Diphosphate↗
PubMed2026

Identification of Drug-resistant Cell Subpopulations in Colorectal Cancer Through Single-cell Analysis and Exploration of Potential Therapeutic Strategies.

INTRODUCTION: The therapeutic efficacy of Colorectal Cancer (CRC) is often compromised by resistance to the standard chemotherapy agent oxaliplatin. METHODS: This study obtained single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) between resistant and sensitive epithelial subpopulations were identified, followed by enrichment analysis. Pseudotemporal trajectory and cell-cell communication were analyzed using Monocle2 and CellChat, respectively. The candidate drug was predicted by Connectivity Map (cMAP) analysis. External validation included assessment of the EpC2 signature in an oxaliplatin-resistant cell line dataset (GSE76092), survival analysis using The Cancer Genome Atlas (TCGA) cohorts, and re-analysis of the GSE179784 dataset to assess the reproducibility of EpC2-like subpopulations and their DNA Damage Repair (DDR) scores. RESULTS: Cell subpopulations were divided into 10 clusters. Among them, epithelial cells comprised 5 subpopulations, with EPC2 identified as a potential oxaliplatin-resistant subset. DEGs were enriched in the TNF and IL-17 pathways. External validation confirmed the enrichment of EpC2 in resistant cell lines and its association with poor survival. Pseudotemporal trajectory revealed that epithelial cells underwent state transitions, forming two distinct branches. The resistant group exhibited enrichment in RNA splicing and NF-κB pathways. Cell-cell communication analysis revealed interactions involving MDK- NCL and PPIA-BSG. Dasatinib was predicted as a candidate drug. DISCUSSION: We identified an oxaliplatin-resistant subpopulation of Epithelial Cells (EpC2) in CRC, elucidated its multi-layered resistance mechanisms, and integrated multi- omics and cMAP database analyses to predict a potential intervention drug. CONCLUSION: This study provided potential therapeutic possibilities for oxaliplatin resistance, contributing to CRC treatment.

Humans↗
PubMed1979

Functional consequences of agonist-mediated state transitions in the cholinergic receptor. Studies in cultured muscle cells.

Parameters associated with activation and desensitization of the nicotinic receptor in the BC3H-1 muscle cell line have been compared with the state transitions that result upon combination with agonist. 125I-labeled cobra alpha-toxin is found to bind to an apparent single class of surface nicotinic receptors on the cells in situ with a rate constant of 1.15 x 10(5) M-1 s-1. The competition between cholinergic ligands and alpha-toxin reveals that agonists, but not classical antagonists, will promote a slow conversion to a receptor state where the affinity for agonists is enhanced. Moreover, agonists such as carbamylcholine elicit a permeability increase to 22Na+ ions that slowly decrements at a rate and to an extent closely paralleled by the conversion of the receptor to the high affinity state. Upon removal of the agonist, both the affinity increase and the diminished permeability change are completely reversible and again exhibit similar kinetics for their return to the original state. A comparison of the capacity of full agonists to compete with alpha-toxin binding and elicit a permeability change suggests that in the absence of agonist, receptor predominates in a low affinity activatable state. Binding of agonists to the low affinity state exhibits little if any cooperativity (n = 0.97 to 1.31), while the corresponding permeability change appears more cooperative (n = 1.31 to 1.52). By contrast, when receptors have been previously equilibrated with agonists, occupation of the receptor occurs over a 3- to 5-fold lower concentration range. Binding following equilibration closely correlates with a concomitant decrease in activatable receptor resulting from equivalent exposure to agonist. Furthermore, under equilibrium conditions, the binding of full agonists is typified by a moderate degree of homotropic cooperativity (1.25 to 1.44), enabling the receptor to desensitize over a narrow range of agonist concentration. Simultaneous measurement of occupation and activation parameters has enabled us to compare a state function for desensitization which is generated from binding parameters with the reduction in permeability seen in the desensitization process. A scheme describing the association of agonist with two functionally distinct receptor states is developed to account for the cooperative relationship between agonist binding and desensitization of the receptor.

Animals↗
PubMed1979

Regulation of dihydrofolate reductase synthesis in an overproducing 3T6 cell line during transition from resting to growing state.

We have isolated a methotrexate (MTX)-resistant clone of mouse 3T6 cells, designated M50L3, which grows normally in the presence or absence of 50 muM MTX and produces a level of dihydrofolate reductase (DHFR; 5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase, EC 1.5.1.3) that is increased about 300-fold compared to the parental 3T6 cells. The cells retain the ability to rest in the G(0) state when maintained in medium containing 0.5% calf serum and can be stimulated to reenter the cell cycle by increasing the serum concentration to 10%. The rate of accumulation of DHFR in resting M50L3 cells is about 1/25th of that in exponentially growing cells. When resting cells are stimulated to reenter the cell cycle, the rate of accumulation of DHFR starts to increase at about 8 hr and reaches a maximum (25-fold increase) at about 16 hr after stimulation. Pulse-labeling experiments show that the increase in DHFR accumulation is due to an increased rate of synthesis. This increase occurs at about the same time the cells enter S phase. However, inhibitors of DNA synthesis have no effect on the increase in DHFR accumulation after serum stimulation, indicating that there is no tight coupling of the two events. Actinomycin D inhibits the subsequent increase in DHFR accumulation if added 8 hr after stimulation but has no effect if added 16 hr after stimulation. This is consistent with the idea that the increase in DHFR gene expression depends on transcription of the gene and that DHFR mRNA synthesis begins at about the time the cell initiates DNA replication. DHFR gene expression appears to be regulated in the same manner in the overproducing cells as we found in the parental 3T6 cells [Johnson, L. F., Fuhrman, C. L. & Wiedemann, L. M. (1978) J. Cell. Phys. 97, 397-406]. Therefore, the alterations that are responsible for DHFR overproduction (presumably DHFR gene amplification) do not interfere with the ability of the cell to regulate the rate of synthesis of the enzyme after serum stimulation.

Animals↗
PubMed1975

[Genesis of islands in the human placenta].

A fetal origin of the isalnds was supposed after light microscopical observations, investigated especially on young placentas. Electron microscopical examination confirm this supposition. The following facts prove, that the islands are products of the trophoblast: 1. The development of Langhans-cells to the differentiated cytotrophoblast, passing the state of the transitional cell type - I have called the differentiated cytotrophoblast "trophocyte". 2. The linkage of the trophocyte to the syncytiotrophoblast of the islands by desmosomes. 3. Definite morphological differences between the trophocytes and the decidual cells. 4. The absence of connective tissue and vessels in the islands.

Chorion↗
PubMed1978

Fluctuations in the production of specific cellular peptides during the growth of animal cells.

Patterns of newly synthesized proteins of Vero cells in different growth states were obtained using two-dimensional gel electrophoresis. The 240 most prevalent peptide spots were then compared. Cells in exponential growth and in the stationary phase were found to have patterns of peptide spots characteristic of their state of growth. The transition between these patterns is progressive, and the cells acquire a pattern characteristic of quiescent cells by the late exponential phase. These observations suggest that a series of modulations in gene expression occurs during the transition of growth states in animal cells that leads to the specific appearance or disappearance of certain cellular peptides.

Animals↗
PubMed1979

Effects of in vivo priming on in vitro induction of cytotoxicity. I. Non-specific augmentation by in vivo presensitization with allogeneic or xenogeneic cells.

In vivo presensitization of donor mice of responding cells with third party cellular antigens augmented in vitro generation of cytotoxic T lymphocytes in allogeneic and xenogeneic combinations. In vitro induction of detectable cytotoxicity in presensitized responding cells required the incubation period needed for in vitro primary response. However, such cytotoxic T lymphocytes were generated after in vitro stimulation with monolayers of methylcholanthrene-induced tumor cells, UV-irradiated or heated spleen cells which had proved to be effective in secondary but not in primary response. Presensitized responding cells exposed to 600R-irradiation did not augment in vitro induction of cytotoxicity in normal responding cells. The augmenting effect of presensitized responding cells may be attributable to radiosensitive T cells which are in a transitional state in differentiation from typical unprimed cells to typical primed cells.

Animals↗
PubMed1977

[The so-called sweat-gland carcinoma of the human breast. A review (author's transl)].

The term sweat-gland carcinoma of the breast is used in widely different meanings. Nonetheless, two histologically well-characterized types may be recognized: 1. The apocrine (oncocytic) carcinoma is composed of large well-delimited cells with finely granular, oxyphilic cytoplasm similar to that of oncocytes of other organs. They resemble the "pale" oxyphilic cells of the aging normal breast whose cytoplasm in part show the same quality. These carcinoma cells are regarded as mammary cells in a state of transition into oncocytes. Any similarity they have to cells of the apocrine axillary sweat-gland is purely superficial and in no way influences the interpretation of apocrine carcinomas. 2. The secreting carcinoma histologically is reminiscent of the functioning, hormonally stimulated breast of pregnancy. It reveals apocrine extrusion of nuclei and an accumulation of neutral fat in cytoplasm and duct lumina. A case of secreting carcinoma is described in detail to exemplify the association with exogenous hormonal stimulation. Both types of differentiation of carcinomas may arise together or with other types of mammary carcinomas, and share the clinical prognosis with them. The term sweat-gland carcinoma of the human breast should be abolished since there exists no proof that they really occur.

Aged↗
PubMed1978

Resting-proliferative transition in cultured mammalian cells.

Cell lines established in culture have been tested for their ability to enter a resting state upon serum step-down. The reentry of resting cells into a proliferative state has been studied. This transition between states of resting and of proliferation is considered a manifestation in cell cultures of physiologic growth regulatory mechanisms. The regulatory effects of hormones and hormone-like peptide growth factors on the resting-proliferative transition are analyzed.

Adrenal Glands↗