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Cell differentiation during fruiting body formation in polysphondylium pallidum.

The spatial pattern of cellular differentiation was studied during fruiting body formation in Polysphondylium pallidum using 3 different staining methods: Calcofluor fluorescence (cellulose accumulation), neutral red (prestalk cells) and immunofluorescence (prespore cells). Neutral-red staining revealed the existence of a clear prestalk region which becomes evident during aggregation and continues throughout culmination. Immunofluorescent staining demonstrated that cells in the prestalk region gradually lose their presporeness (fluorescence) as they are transformed into differentiated stalk cells. Calcofluor staining revealed that stalk cell differentiation begins during the mid-aggregation phase and that the mode of formation of the main stalk and the side branches differs slightly in morphology. Calcofluor staining also demonstrated the development, during aggregation, of a thick cellulosic girdle with lateral tubular extensions which surround the aggregation streams. The above results are discussed in terms of our present knowledge about differentiation and morphogenesis in cellular slime moulds.

Dictyostelium

RNA synthesis and changes in template--DNA activity during the growth and differentiation of parenchyma cells of the primary cortex of roots of Zea mays and Tulipa kaufmanniana.

In this study, changes in DNA transcription activity are presented during parenchymal cell differentiation of the primary cortex of roots of a species with elevated DNA content in which endomitotic polyploidization does not occur (Tulipa kaufmanniana), as well as a species with low content levels in which an increase in endomitotic polyploidization occurs during differentiation (Zea mays). Changes in the degree of histone acetylation during the cellular differentiation of both species were also studied. An autoradiographic method was employed using the following indicators: for transcription activity--3H-uridine; for potential activity of template DNA--3H-actinomycin D (3H-AMD); for histone acetylation--the intensity of labelled nuclei after incubation with 3H-sodium acetate, as well as decrease in nuclei radioactivity after extraction of the histone fractions. It was found that during cellular growth and differentiation in both Zea mays and Tulipa daufmanniana (and therefore, irrespective of the presence or absence of endomitotic polyploidization) a progressive decrease of DNA transcription activity occurs. At the same time, the possibility that the acetylation of arginine--rich histones plays a definite, yet undecisive, role in the regulation of DNA transcription activity cannot be excluded.

DNA

Integrator promotes the association of TFIID and RNA polymerase II to maintain pluripotency during development.

The mechanisms by which the expression of pluripotency and Polycomb networks are harmonized to allow the transition from pluripotency to a differentiated state have not been fully elucidated. Integrator complex regulates transcription pause release and RNA processing in metazoans. We show that Integrator is required for stemness and plays a critical role as early as day 2 in embryonic development. While the catalytic endonuclease activity enhances cellular reprogramming, Integrator recruits RNA polymerase II (RNAPII) to promoters and super enhancers of pluripotency and Polycomb genes. Integrator coordinates expression of pluripotency and Polycomb networks by fostering the association of RNAPII and basal transcription factors. We pinpoint a critical role for TATA-binding protein-associated factors (TAFs) in Integrator entry into the preinitiation complex. Taken together, beyond its role in RNAPII pause release, Integrator recruitment of RNAPII ensures an orderly cellular differentiation during development.

RNA Polymerase II

The cellular aging of rat fibroblasts in vitro is a differentiation process.

Cellular aging of diploid rat fibroblasts in vitro occurs as the result of a three-stage differentiation sequence, taking place in the morphologically recognizable differentiating cell compartment of the fibroblast stem cell system. Simultaneously with an age-dependent morphological differentiation there is an age-dependent biochemical differentiation of the fibroblasts. In cell strains with the genetic background Lewis, the cellular differentiation state, the major histocompatibility complex composition (H-1) and the H-1 complex-controlled expression of endogenous type C viruses determine the ultimate fate of the senescent cell, leading either to cellular degeneration or to cellular neoplastic transformation.

Animals

Dynamics of skeletal pattern formation in developing chick limb.

During development of the embryonic chick limb the skeletal pattern is laid out as cartilaginous primordia, which emerge in a proximodistal sequence over a period of 4 days. The differentiation of cartilage is preceded by changes in cellular contacts at specific locations in the precartilage mesenchyme. Under realistic assumptions, the biosynthesis and diffusion through the extracellular matrix of a cell surface protein, such as fibronectin, will lead to spatial patterns of this molecule that could be the basis of the emergent primordia. As cellular differentiation proceeds, the size of the mesenchymal diffusion chamber is reduced in descrete steps, leading to sequential reorganizations of the morphogen pattern. The successive patterns correspond to observed rows of skeletal elements, whose emergence, in theory and in practice, depends on the maintenance of a unique boundary condition at the limb bud apex.

Animals

[Functional and morphologic characteristics of limbic cortex maturation during early ontogenesis].

Development of the limbic cortical area in postnatal ontogenesis of the rabbit comprises three periods judging by the parameters of impulse activity of neurones and cytoarchitectonic differentiation. The period of stratification and beginning of cellular differentiation functionally corresponds to the manifestation of simple forms of spike activity (single, group) with long inactivation periods (the first week of life). The period of intensive cytoarchitectonic differentiation with separation of the agranular type of the anterior limbic area structure correlates with a more complex neuronal impulse activity (burst discharges), augmenting spectrum of dominating spike frequencies, predominance of phasic activation and specific responses together with a high total neuronal responsiveness to sensory (acoustic) stimuli (the second to third week of life). The period of complete cytoarchitectonic maturation corresponds to the stabilization of functional properties of neurones (the fourth to sixth week of life). The revealed ontogenetic dynamics of morpho-functional reorganizations in the limbic cortex point to its involvement at an early stage of postnatal life in the mechanisms of sensory analysis and of the formation of adequate adaptive reactions.

Age Factors

The development of the pattern of growth.

It is proposed that the varying patterns of growth in development can be viewed as an aspect of pattern formation, and that different growth programmes are specified at an early stage. This is illustrated largely with respect to the development and growth of the chick wing. The spatial pattern of cellular differentiation and programme for growth can be considered in terms of the concept of positional information. The lengths of the cartilaginous elements are determined by the initial length of the primordium and its later growth, involving cell multiplication enlagement and matrix secretion. It seems that tissues have a high degree of autonomy with respect to differentiation and growth after they have had their position specified. The cellular basis of programmed growth is discussed.

Animals

[Critical study of the morphogenesis of trunco-conal malformations].

Anatomical and angiocardiographic studies have made possible discussion of hypotheses of the development and differentiation of the conus and of the trunco-conal orientation of the septum. Three autopsy specimens and two angiocardiogrammes of intertwined great vessels with transposition and partial distortion of the great vessels were studied. The specimen of intertwined great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum. In the case of transposition the opposite situation was encountered with a muscular pulmonary infundibulum posterior to and greater than the sub-aortic infundibulum; the plane of the aortic valves was higher than that of the pulmonary valves. The specimen of partial distortion of the great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum with the aortic valve set higher and in fibrous continuity with the mitral valve. It is concluded that the relations of the great vessels between each other and with the ventricles depend on the orientation of the trunco-conal septum and on the process of incorporation of the cone. The presence or absence of a posterior muscular infundibulum is not related to the growth or differential reabsorption of the cone but to a process of cellular differentiation. There was no relation between the level of the valves and their spatial orientation and the length of the infundibulum. The continuity or discontinuity between the aortic and atrio-ventricular valves is not determined by the level of the aortic valves.

Female

The cytological differentiating potential of pineal parenchymal neoplasms (true pinealomas). A clinicopathological study of 28 tumours.

A series of 28 pineal parenchymal tumours is described, with special reference to the potential of some of these neoplasms to differentiate along glial or ganglionic lines, or both. The more undifferentiated tumours (pineoblastomas, 11 cases) were the most frequent: they are histologically similar to medulloblastomas. One example showed focal differentiation to retinoblastoma at the primary site. The histological features of pineoblastomas merged with those of pineocytomas (7 cases), in which the lobular architecture is reminiscent of that of the mature pineal gland. In addition, 10 further examples in the group of pineocytomas showed more advanced differentiation as follows: towards astrocytes only (2 cases), towards ganglion cells only (1) case) and towards both astrocytes and ganglion cells (gangliogliomas) (7 cases). Confirmation of the pineal parenchymal nature of these neoplasms and of their differentiating potential was provided by a modification of the Achúcarro-Hortega's silver carbonate impregnation technique for pineal parenchymal cells, by specific silver impregnations for axonal processes, and by an immunoperoxidase stain for glial fibrillary acidic (GFA) protein. Electron microscopy of one new example of pineocytoma with neuronal and astrocytic differentiation demonstrated the presence of numerous microtubules, of clear-centred and dense-core vesicles, and of synaptic complexes. Seven illustrative clinical histories with pathological findings are presented. The identification of special features of cellular differentiation is of importance in evaluating the biological behaviour of these neoplasms since a definite correlation can be established between the patient's age, some of the cytological variants, and the malignant potential of the tumour. Pineoblastomas are highly malignant neoplasms of children and young adults which disseminate widely throughout the cerebrospinal fluid pathways. -ineocytomas without cellular evidence of further differentiation occur at any age and are also clinically malignant, but with a somewhat lesser tendency to metastasize than pineoblastomas. Pineobytomas with astrocytic differentiation occur in adults and may be either slowly growing or malignant. Pineocytomas with neuronal or with neuronal and astrocytic differentiation occur in later life, remain localized, and are relatively benign. Since the latter account for approximately one-third of pineal parenchymal tumours and are likely to be relatively radio-resistant, tissue diagnosis is imperative for a determination of the therapeutic approach. Radiation to the entire neuraxis should be administered to patients with pineoblastomas and malignant pineocytomas in view of their high frequency of cerebrospinal metastasis. An accurate histological classification of these tumours therefore carries important clinical and therapeutic implications...

Adolescent

[Correlations between the processes of cell differentiation and development of blood vessels in the (chick embryo) adenohypohhysis].

Utilizing semi-thin and, respectively, thick sections after indian ink injections, we have analyzed morphohistogenesis and vessel development in the adenohypophysis of chick embryos from the 4th to the 19th incubation day. Our preliminary results indicate that a close correlation exists between cellular differentiation and vasculogenesis. Vessels begin to enter the gland only at the 6th day when the first endocellular granules become detectable, and, from the 10th day, they markedly increase in number and size, gradually acquiring a peculiar sinusoidal arrangement around cellular groups, as cell differentiation further progresses.

Animals

Plasma membrane phospholipid, cholesterol and fatty acyl composition of differentiated and undifferentiated L6 myoblasts.

The lipid composition of plasma membranes isolated from differentialted and undifferentiated L6 myoblasts have been compared. In general, the plasma membranes of differentiated L6 myoblasts have a higher cholesterol to phospholipid molar ratio than plasma membranes of undifferentiated cells. Differentiated L6 myoblasts have increased relative amounts of phosphatidylethanolamine and phosphatidylcholine ine in their plasma membrane and a decreased relative amount of sphingomyelin when compared with the plasma membranes of undifferentiated myoblasts. In addition, preliminary results show that differentiated L6 myoblasts plasma membrane phospholipid shows differences in the fatty acyl composition, specifically there appears to be relatively more 17:0 and 24:1 and less 16:1 and 18:1 than in plasma membrane phospholipids of undifferentiated L6 myoblasts. These observations indicate that significant changes in plasma membrane lipid composition occur during myoblast differentiation. The role that changes in lipid composition play in control of cellular differentiation, however, remains to be elucidated.

Cell Differentiation

Dibutyryl cAMP-induced protein changes in differentiating mouse neuroblastoma cells.

Proteins from mouse neuroblastoma cells treated with dibutyryl adenosine-3',5'-monophosphate (B2cAMP) were analyzed by high resolution, two-dimensional gel electrophoresis. Quantitative changes in proteins and charge modifications of proteins apparently induced B2cAMP were detected by isoelectric focusing. Some proteins appeared to be modified and one protein was increased 7- to 8-fold in cells treated with B2cAMP. Since neuroblastoma cells differentiate when treated with B2cAMP, understanding the protein changes induced by B2cAMP may help to understand cellular differentiation in neural tissue.

Animals

A single-nucleus and spatial transcriptomic atlas of poplar leaves reveals the regulation of leaf polarity and cuticle deposition.

Leaf adaxial-abaxial polarity is fundamental for plant morphogenesis and environmental adaptation through asymmetric cell differentiation. Emerging evidence reveals dorsoventral metabolic gradients act downstream of transcriptional networks to fine-tune cellular specialization. While conserved transcription factors (e.g., HD-ZIP III and KANADI) establish initial polarity, the molecular networks driving position-specific cellular differentiation and their integration with metabolic adaptation remain unclear. Leveraging single-nucleus and spatial transcriptomics, we resolve major cell classes (mesophyll, epidermal, and vascular-associated) and their adaxial-abaxial subtypes, revealing dorsoventral polarity in transcriptional profiles and metabolic pathways. Adaxial cells are enriched in phenylpropanoid/flavonoid biosynthesis, while abaxial cells show preferential activation of stress and hormone signaling. Notably, we identify MYC2 as a key regulator of adaxial cuticle biosynthesis, binding to promoters of lipid biosynthetic and transport genes (e.g., CER10 and LTPG1) and promoting cuticle thickening. Our study uncovers how positional identity shapes transcriptional and metabolic polarity in leaves, with MYC2 emerging as a central regulator coordinating organ-specific adaptations. These findings provide insights into the spatial regulation of plant development and stress resilience, offering potential strategies for engineering stress-tolerant woody crops.

Plant Leaves

Differentiation of mouse neuroblastoma cells in vitro and in vivo induced by cyclic adenosine monophosphate (cAMP).

The murine neuroblastoma appears to be a useful model for elucidating the mechanism of cellular differentiation. In tissue culture, MNB cells were induced to "irreversibly" differentiate into neuronal-like cells by DBcAMP alone or in combination with cAMP phosphodiesterase inhibitors: papaverine (Pap) and theophylline (Theo). Cells differentiated by DBcAMP, Pap, and Theo were no longer tumorgenic when reinoculated into animals of the host strain. In vivo, DBcAMP, Pap, and Theo caused a reduced tumor volume growth rate in animals with established tumors. Morphologically, this effect appears to be secondary to an arrest of cellular mitoses. Cells insensitive to these agents emerged after 3 to 4 days, and tumor growth accelerated to parallel the rate of the untreated tumors.

Adenosine Monophosphate

Cell population kinetics of 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse.

The parameters of cell population kinetics of symmetrical 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse were analyzed using the fraction labeled-mitoses curve method and compared with those of three groups of epithelial cells in the crypt of the descending colon of normal mouse. The analysis of three groups of epithelial cells in the crypt of normal mouse indicates that differentiation of epithelial cells was associated not only with a smaller proliferative pool of cells but also with a shortening of the duration of G2 phase and a prolongation of mitotic time. Other parameters of cell cycle did not change significantly. The mean cell cycle time of neoplastic cells in chemically induced colonic neoplasms was similar to that of epithelial cells in normal colon, but the variance was much greater in neoplastic cells. In neoplastic cells, the proliferative pool was greater, the G1 phase prlonged, and the S phase and the mitotic time became shorter as compared to epithelial cells in normal colon. The duration of G2 phase of neoplastic cells fell between the values of presumptive stem cells and differentiating cells in normal colon, compatible with the hypothesis that neoplastic cells are transformed stem cells defective in cellular differentiation. In the colonic mucosa immediately adjacent to neoplasms, the fraction-labeled-mitoses curve showed a flat second wave, indicating that the group of cells initially labeled by the pulse became a mixture of cells, some continuing the proliferative cycle normally, some going out of cycle, some slowing down in their passage from S through G2 to M, and some being arrested in mitotic phase. Such heterogeneous behavior of cells may be closely related to expansion of neoplasms. With some assumptions, however, cell cycle parameters of those normally cycling cells were estimated: the cell cycle time and the duration of G1 phase and mitotic phase were prolonged as compared to neoplastic cells and epithelial cells of normal colon.

Adenocarcinoma