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Results for “Stem cell differentiation”

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At least 19 recordsLinked to original sources
PubMed1979

[Factors that control the differentiation of stem cells. I. The change in direction of hematopoietic stem cell differentiation under the effect of differentiating T-lymphocytes].

A mixed transplantation of bone marrow cells, and lymph nodes or thymic cells of mice CBA strain into lethally irradiated hybrid recipients (CBAXC57B1)F1 is accompanied with changes in the differentiation pattern from a mainly erythroid to a mainly granuloid way. Thymectomy of either donor of bone marrow cells or recipients, or both, destroys the stem cell differentiation in the direction of granulopoieseis. Intact syngeneic lymphocytes normalize differentiation of the stem cells, but in the presence of tissue antigens these provide for the stem cell differentiation mainly in the direction of granulopoiesis. The differentiation of stem haemopoietic cells is accomplished under the thymic and lymphocyte control. T-differentiating lymphocytes (Td) are the lymphocytes controlling the stem cell differentiation.

Animals↗
PubMed2026

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface-Condensate Trajectory.

Stem cells exhibit exceptionally prominent transcriptional clusters, which dissolve with progressing differentiation. Although these clusters are assigned central roles in embryonic gene regulation, their formation and loss during differentiation remain poorly understood. This study reveals that these prominent clusters disperse along a conserved trajectory in mouse embryonic stem cells, fruit fly testes, and zebrafish embryos. Imaging and lattice simulations show that these clusters form via surface condensation on H3K27ac-marked super-enhancer regions, which act as genomic scaffolds. Upon differentiation, partial loss of these active epigenetic marks and transcription-driven unfolding lead to dispersal of the prominent clusters. The block copolymer-based lattice simulations explain this process as a conserved trajectory through a three-dimensional state space, governed by surface condensation principles that extend beyond canonical liquid-liquid phase separation. This work marks surface condensation as a biophysical mechanism for the dynamic organization of stem cell-specific transcriptional hubs and demonstrates evolutionary conservation in several organisms. By uncovering a conserved biophysical mechanism for transcriptional organization in development, our work illustrates how polymer properties can contribute to the control of cell identity and fate.

Animals↗
PubMed1979

Humoral regulation of pluripotent stem cell differentiation.

Humoral regulators of CFU-S differentiation have been demonstrated in bone marrow of Ara-C treated animals. These factors are effective in vivo and are also capable of inducing erythropoietic differentiation of normal CFU-S in vitro. These results seem to indicate that the microenvironment acts at the committed stem cell level while the factors described in this paper act on the pluripotent stem cells.

Animals↗
PubMed2026

Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke.

Stroke remains a leading cause of long-term neurological disability worldwide, largely due to irreversible neuronal loss and the limited regenerative capacity of the adult mammalian brain. Neural stem cells (NSCs) in the adult brain possess the potential to generate new neurons after injury, yet the molecular mechanisms regulating their neuronal differentiation following ischemic insult remain incompletely understood. Here, integrating single-cell multi-omics analyses with spatial transcriptomics, we systematically delineated cell type-specific spatiotemporal dynamics in the striatum of a mouse model of ischemia-reperfusion injury. We identified Neurensin 1 (Nrsn1) as a gene markedly upregulated during NSC-derived neuronal differentiation in the recovery phase. Mechanistically, Foxa2 directly activates Nrsn1 transcription, whereas Nrsn1 promotes neuronal differentiation by facilitating the nuclear translocation of the chromatin-remodeling factor Smarcc1 in vitro. In vivo, both endogenous NSCs and transplanted NSCs overexpressing Nrsn1 significantly enhanced neuronal regeneration and improved functional recovery in mice subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Collectively, these findings identify Nrsn1 as a key regulator of NSC neuronal differentiation and uncover a Nrsn1-Smarcc1 coupling mechanism that promotes neural regeneration after ischemic brain injury, highlighting a potential molecular target for strategies aimed at enhancing post-stroke recovery.

Foxa2↗
PubMed2026

Biomimetic Hydrogels with Nucleus Pulposus-like Viscoelasticity and ECM Peptides for Discogenic Differentiation of Stem Cells.

Intervertebral disc (IVD) degeneration is a leading cause of low back pain (LBP), primarily originating in the nucleus pulposus (NP). Regenerative strategies combining mesenchymal stem cells (MSCs) with biomaterials offer great potential for NP repair by replenishing cells and restoring extracellular matrix (ECM). However, key translational challenges remain, including limited stem cell differentiation, poor cell survival in the harsh degenerative niche, and insufficient biomaterial support. While matrix viscoelasticity has been shown to influence adipose-derived stem cell (ASC) discogenic differentiation, its interplay with cell-adhesive ligands for IVD regeneration remains unclear. Moreover, most current hydrogels fail to replicate the ultrafast stress relaxation properties of native non-degenerative human NP tissue. Here, we developed viscoelastic ECM peptide-functionalized hydrogels (VEPH), specifically designed to mimic healthy human NP biomechanics and promote ASC differentiation for NP regeneration. We biochemically conjugated NP ECM-derived adhesive peptides (IKVAV, hA5G26, CHAD) through maleimide-thiol click chemistry, achieving hydrogels with significantly faster stress relaxation (∼25 s) compared to conventional viscoelastic alginate hydrogels (>100 s). Our results demonstrated that VEPH supported >95% ASC viability and robust metabolic activity over 21 days in 3D culture. Notably, the IKVAV-functionalized hydrogel significantly enhanced ASC cell-matrix interactions, upregulated NP marker expression (KRT18, HIF-1α, ITGA3, and CD24), and promoted type-II collagen secretion, indicating an NP-committed cell fate. Our findings highlight the synergistic roles of matrix viscoelasticity and NP-specific biochemical cues in directing ASC discogenic differentiation and advancing novel biomaterial design for IVD regeneration.

cell-adhesive peptides↗
PubMed2025

Temporal multiomics gene expression data of human embryonic stem cell-derived cardiomyocyte differentiation.

Human embryonic stem cells (hESCs) serve as a valuable in vitro model for studying early human developmental processes due to their ability to differentiate into all three germ layers. Here, we present a comprehensive multi-omics dataset generated by differentiating hESCs into cardiomyocytes via the mesodermal lineage, collecting samples at 10 distinct time points. We measured mRNA levels by mRNA sequencing (mRNA-seq), translation levels by ribosome profiling (Ribo-seq), and protein levels by quantitative mass spectrometry-based proteomics. Technical validation confirmed high quality and reproducibility across all datasets, with strong correlations between replicates. This extensive dataset provides critical insights into the complex regulatory mechanisms of cardiomyocyte differentiation and serves as a valuable resource for the research community, aiding in the exploration of mammalian development and gene regulation.

Humans↗
PubMed2025

Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells.

Cell differentiation results from coordinated changes in gene transcription in response to combinations of signals. Fibroblast growth factor (FGF), Wnt and mammalian target of rapamycin (mTOR) signals regulate the differentiation of pluripotent mammalian cells towards embryonic and extraembryonic lineages, but how these signals cooperate with general transcriptional regulators is not fully resolved. Here, we report a genome-wide CRISPR screen that reveals both signaling components and general transcriptional regulators for differentiation-associated gene expression in mouse embryonic stem cells (mESCs). Focusing on the Mediator subunit-encoding Med12 gene as one of the strongest hits in the screen, we show that it regulates gene expression in parallel to FGF and mTOR signals. Loss of Med12 is compatible with differentiation along both the embryonic epiblast and the extraembryonic primitive endoderm lineage but impairs pluripotency gene expression and slows down transitions between pluripotency states. These findings suggest that Med12 helps pluripotent cells to efficiently execute transcriptional changes during differentiation, thereby modulating the effects of a broad range of signals.

Animals↗
PubMed2025

A pluripotent stem cell atlas of multilineage differentiation.

Human pluripotent stem cells offer a scalable platform to study genetic and signalling mechanisms governing cell lineage decisions during differentiation. Genome-wide and single-cell transcriptomics technologies likewise offer high-throughput analysis of heterogeneous cell differentiation states. While in vivo development has been extensively characterised using these technologies, there remains a need for comprehensive single-cell transcriptomic profiling of stem cell differentiation from pluripotency. Understanding gene expression changes governing differentiation in vitro is key to developing high fidelity differentiation protocols and understanding fundamental mechanisms of development. We generated a single-cell RNA sequencing time course to study the role of developmental signalling pathways on multilineage diversification from pluripotency in vitro. The combined dataset of over 60,000 cells spans cell types from a time course of differentiation across all germ layers, ranging from gastrulation cell states to progenitor and committed cell types. These data provide a diverse benchmarking reference point to compare against in vivo development and advance understanding of signalling regulation of differentiation, providing insights into protocol development, drug screening, and regenerative medicine applications.

Pluripotent Stem Cells↗
PubMed1979

[Factors controlling the recirculation of hematopoietic stem cells. IV. The effect of thymosin on the migration and differentiation of hematopoietic stem cells].

Thymosine, a thymus hormone, restores the thymectomy induced deterioration of the routine pathways of migration and differentiation ofhemopoietic stem cells in mice. Administration of thymosine together with bone marrow cells from thymectomized mice to irradiated recipients also restores the level of migration and differentiation of hemopoietic stem cells. The inducing effect of thymosine on the maturation of T-lymphocyte precursors, which in their turn restore the usual rate of migration and differentiation of hemopoietic stem cells, has been suggested.

Animals↗
PubMed1977

Factors controlling stem cell recirculation. III. Effect of the thymus on the migration and differentiation of hemopoietic stem cells.

Experiments were carried out to investigate the effect of thymectomy on the migration and differentiation of hemopoietic stem cells released from shielded parts of bone marrow after irradiation of mice with lethal doses of x-rays. In 2-3 wk after thymectomy, the rate of migration declined and the differentiation of stem cells into granulocytic colonies was inhibited. Transplantation of syngeneic thymus or lymph node cells into thymectomized mice enhanced the migration of stem cells from the bone marrow and restored the usual pathways of their differentiation.

Animals↗
PubMed1977

[Effect of erythrocyte breakdown products on mast cells and erythropoietin formation].

Experiments were conducted on CBA mice and albino rats. A study was made of the effect of erythrocyte destruction products (EDP) on the content of hemopoietic colony-forming units (CFU), differentiation of stem cells and the erythropoietin production. It was shown that 3 or 4 EDP injections to normal mice or to lethally irradiated (1000 rad) mice after the transplantation of bone marrow cells caused no changes in the CFU level of stem cells differentiation. In case of a daily (for 3 days) administration of EDP to mice before the irradiation (1000 rad) and bone marrow transplantation there was observed an increase of the colonies count in the recipients' spleen on account of the erythroid colonies. EDP injection caused no changes in the erythropoietic activity of the blood serum. A possible role of erythrocyte destruction products in the mechanism of erythropoiesis autoregulation is discussed.

Animals↗
PubMed1979

Stem cell growth and differentiation in Hydra attenuata. II. Regulation of nerve and nematocyte differentiation in multiclone aggregates.

The differentiation of nerve cells and nematocytes from interstitial stem cells in Hydra has been investigated under conditions of changing stem cell density. Interstitial stem cells were cultured in a feeder layer system consisting of aggregates of nitrogen mustard-inactivated tissue. The aggregates were seeded with varying numbers of stem cells from 10 to 400 per aggregate; between 4 and 7 days later the rates of nerve and nematocyte differentiation were measured. Nerve differentiation was scored by labelling the stem cell population with [3H]-thymidine and counting nests of 4 proliferating nematoblasts. In both cases the numbers of differentiating cells were normalized to the size of the stem cell population. The results indicate that the rate of nematocyte differentiation increases as the concentration of stem cells increases in aggregates; under the same conditions the rate of nerve differentiation remains essentially constant. To calculate the numbers of stem cells entering each pathway per generation, a computer was programmed to simulate the growth and differentiation of interstitial stem cells. Standard curves were prepared from the simulations relating the rates of nerve and nematocyte differentiation to the fraction of stem cells committed to each pathway per generation. The rates of nerve and nematocyte commitment were then estimated from the experimentally observed rates of differentiation using the standard curves. The results indicate that nerve commitment remains constant at about 0.13 stem cells per generation over a wide range of stem cell concentration. Nematocyte commitment, by comparison, increases from 0.15 to 0.21 stem cells per generation as stem cell concentration increases in aggregates. The fact that the ratio of nerve to nematocyte commitment changes under our conditions suggests that stem cell commitment is not a stochastic process but subject to control by environmental stimuli.

Animals↗
PubMed1978

Embryonic mouse thymus development: stem cell entry and differentiation.

The entry and subsequent division and differentiation of blood-borne stem cells within the embryonic thymus has been studied in a system where the inflowing cells were either chromosomally or antigenically marked. H-2 positive stem cells enter the thymus within 5 days of grafting but may wait for up to 14 days before proliferating to give rise to Thy-1 positive thymocytes.

Animals↗
PubMed1979

Immunoregulation of localized and disseminated murine myeloma: antigen-specific regulation of MOPC-315 stem cell proliferation and secretory cell differentiation.

Tumor development, MOPC-315 stem cells, and M315-secretory cells were quantitated in carrier-primed BALB/c mice that had been challenged subcutaneously or i.v. with mixtures of TNP-carrier and TNP-binding MOPC-315 cells. We observed that tumor incidence, myeloma stem cells, and secretory myeloma cells were: i) suppressed in mice in whom carrier-specific suppressor T cells had previously been induced and ii) initially ehnahced in mice with carrier-specific helper T cells. The early enhancement in mice with carrier-specific helper T cells was followed by progressively declining myeloma stem cell frequencies and regression of established tumors. These studies demonstrate that T cell-derived immunoregulators of host origin can be focused onto localized and disseminated malignant B cells and specifically regulate the expansion and differentiation of the neoplastic clone.

Animals↗
PubMed1978

Regulation of the self-renewal probability in Hydra stem cell clones.

Hydra interstitial stem cells continuously give rise to daughter stem cells as well as precursors for nerve and nematocyte differentiation. Growth of the stem cell population is controlled by the self-renewal probability (Ps): Ps is the fraction of stem cell daughters that remain stem cells in each generation. We have determined Ps for Hydra interstitial stem cells by using a novel technique based on the cell conposition of clones. Stem cell clones were grown in aggregates of nitrogen mustard-inactivated Hydra tissue. They contain several hundred cells after 14 days of growth, including stem cells, differentiating nematocytes, and differentiating nerve cells. Clone size, size variability, and the ratio of differentiating cells to stem cells are sensitive measures of Ps. We have prepared standard curves relating these parameters to Ps, using computer simulations of clone growth. Comparisoon of the experimentally observed parameter of clones to these curves indicates that Ps decreases from 0.8 in 5- to 6-day clones to 0.6 in 10- to 12-day clones. The decrease in Ps coincides with the increase in clone size and suggest that Ps may be regulated by the density of stem cells in clones. Such a mechanism could be responsible for the observed homeostasis of stem cell populations in vivo.

Cell Differentiation↗