Probability that the commitment of murine erythroleukemia cell differentiation is determined by the c-myc level

During the commitment of mouse erythroleukemia cell differentiation, c-myc mRNA levels change dramatically. To examine the involvement of c-myc in the commitment of these cells, we have introduced the rat c-myc gene driven by inducible, heterologous (human metallothionein IIA) gene promoter into murine erythroleukemia cells and we have examined the ability of the transformed cells to undergo commitment to terminal differentiation. The induction of the exogenous c-myc gene expression inhibited the commitment of these cells. Time-dependent inhibition of the commitment was observed with the addition of zinc at an appropriate time after the induction with dimethyl sulfoxide. The result clearly indicated that late decline, not early decline, is required for the commitment. By examining the transformants expressing the exogenous c-myc mRNA at different levels, and the induction of the exogenous c-myc mRNA by varying the concentration of zinc, we demonstrated that the commitment may be determined by a stoichiometric amount of c-myc in the defined period. The data also suggest that the probability value for the commitment process occurring in a stochastic manner is well-correlated with the amount of c-myc mRNA.     

Family planning among Japanese on public relief

Abstract

Two recurrent concepts in fertility literature permit prediction of an inverse relationship between social class and fertility. The commitment to familism refers to the degree that couples embrace a family‐centered style of life over a consumerist or careerist style of life. Commitment to individual children refers to the emotional and material involvement of parents in each child they have. Data show that commitment to individual children is negatively related to fertility, that social class is negatively related to commitment to familism, that social class is positively related to commitment to individual children, and that commitment to familism and commitment to individual children account for relationships between class and fertility.     

Pupal commitment and its hormonal control in wing imaginal discs

The timing of pupal commitment of the forewing imaginal discs of the silkworm, Bombyx mori, was determined by a transplantation assay using fourth instar larvae. The wing discs were not pupally committed at the time of ecdysis to the fifth instar. Pupal commitment began shortly after the ecdysis and was completed in 14 h. When the discs of newly molted larvae (0-h discs) were cultured in medium containing no hormone, they were pupally committed in 26 h. In vitro exposure of 0-h discs to 20-hydroxyecdysone accelerated the progression of pupal commitment. Methoprene, a juvenile hormone analog (JHA), did not suppress the change in commitment in vitro at physiological concentrations. Thus the wing discs at the time of the molt have lost their sensitivity to JH, and 20E is not a prerequisite for completion of pupal commitment. These results suggest that the change in commitment in the forewing discs may begin before the last larval molt.     

The cell cycle of<Emphasis Type="Italic">Chlamydomonas reinhardtii</Emphasis>: the role of the commitment point

Chlamydomonas reinhardtii cells can double their size several times during the light period before they enter the division phase. To explain the role of the commitment point (defined as the moment in the cell cycle after which cells can complete the cell cycle independently of light) and the moment of initiation of cell division we investigated whether the timing of commitment to cell division and cell division itself are dependent upon cell size or if they are under control of a timer mechanism that measures a period of constant duration. The time point at which cells attain commitment to cell division was dependent on the growth rate and coincided with the moment at which cells have approximately doubled in size. The timing of cell division was temperature-dependent and took place after a period of constant duration from the onset of the light period, irrespective of the light intensity and timing of the commitment point. We concluded that at the commitment point all the prerequisites are checked, which is required for progression through the cell cycle; the commitment point is not the moment at which cell division is initiated but it functions as a checkpoint, which ensures that cells have passed the minimum cell size required for the cell division.     

TGF-beta-exposed plasmacytoid dendritic cells participate in Th17 commitment

TGF-β is required for both Foxp3(+) regulatory T cell (Treg) and Th17 commitment. Plasmacytoid DCs (pDC) have been shown to participate to both Treg and Th17 commitment as well. However, few studies have evaluated the direct effect of TGF-β on pDC, and to our knowledge, no study has assessed the capacity of TGF-β-exposed pDC to polarize naive CD4(+) T cells. In this paper, we show that TGF-β-treated pDC favor Th17 but not Treg commitment. This process involves a TGF-β/Smad signal, because TGF-β treatment induced Smad2 phosphorylation in pDC and blockade of TGF-β signaling with the SD208 TGF-βRI kinase inhibitor abrogated Th17 commitment induced by TGF-β-treated pDC. Moreover, TGF-β mRNA synthesis and active TGF-β release were induced in TGF-β-treated pDC and anti-TGF-β Ab blocked Th17 commitment. Unexpectedly, TGF-β treatment also induced increased IL-6 production by pDC, which serves as the other arm for Th17 commitment driven by TGF-β-exposed pDC, because elimination of IL-6-mediated signal with either IL-6- or IL-6Rα-specific Abs prevented Th17 commitment. The in vivo pathogenic role of TGF-β-treated pDC was further confirmed in the Th17-dependent collagen-induced arthritis model in which TGF-β-treated pDC injection significantly increased arthritis severity and pathogenic Th17 cell accumulation in the draining lymph nodes. Thus, our data reveal a previously unrecognized effect of TGF-β-rich environment on pDC ability to trigger Th17 commitment. Such findings have implications in the pathogenesis of autoimmune diseases or immune responses against mucosal extracellular pathogens.     

Commitment to Division in Ciliate Cell Cycles

Near the end of the cell cycle, ciliates commit irreversibly to cell division. The point of commitment occurs at the time of oral polykinetid assembly and micronuclear anaphase. The commitment is a checkpoint which requisites a threshold cell mass/ DNA ratio and stomatogenesis. It is also a physiological transition point, involving cdk protein kinases similar to those of other eukaryotes. Both P34 kD and P36 kD kinases, similar to the S. pombe cdc2 kinases, have been described to have activity as monomers. Subsequent to commitment to division, dramatic cytoskeletal modifications occur for separation of organelles, cortex morphogenesis and cytokinesis. Numerous mutants affecting cytoskeletal function associated with the division process have been obtained in several species. Of these, only the ccl mutant in Paramecium affects cell cycle progression prior to commitment to division. The material reviewed is used to speculate about the mechanisms of regulation of pre-fission morphogenesis and cell division related processes in ciliates.     

Regulation of the commitment processes in the hematopoiesis

Various methods of commitment regulation have been analysed on the basis of the mathematical model of the haemopoietic stem cell number dynamics. The starting point is the requirement on the system stability. The basic hypothesis is that of the intrinsic nature of the population commitment regulation. The analysis states that the commitment specific velocity increases with stem cell number. This way of regulation may be performed in the case the commitment takes place at Go phase of the cell cycle. The role of the committed precursor pool in providing the haemopoietic system reliability is discussed.     

Lithium inhibits terminal differentiation of erythroleukemia cells : Evidence for a pre-commitment ‘priming’ event

Lithium has been found to be a novel inhibitor of the terminal differentiation of Friend murine erythroleukemia cells. A general method for the quantitative analysis of differentiation inhibitors has been developed and used to compare the site of inhibition by lithium with that by vanadate. Lithium inhibits the commitment to differentiation (K 1/2 approximately 10 mM) induced by DMSO (dimethylsulfoxide) at non-toxic concentrations that have only a small effect on the rate of proliferation. Inhibition is reversible and probably requires entry of Li+ into the cell, since it is blocked by high KCl in the medium. LiCl is most effective when present during the first 10 h of DMSO treatment, before commitment is initiated. Computer-assisted analysis of the kinetics of commitment demonstrate that inhibition by lithium is best described by including a lithium-sensitive 'priming' event, which occurs with high probability prior to commitment.     

Effects of protein kinase A and calcium/phospholipid-dependent kinase modulators in the process of HL-60 cell differentiation: their opposite effects between HL-60 cell and K-562 cell differentiation.

We have previously shown that HL-60 cells treated with 1 alpha, 25-(OH)2D3 in magnesium-deficient medium are committed to differentiate but do not express differentiation-related phenotypes. In the present study, we demonstrated that Mg2+ deprivation blocked the process of differentiation before the induction of lysozyme mRNA and that the process of HL-60 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step. We studied the effects of protein kinase A (PKA) and calcium/phospholipid-dependent protein kinase (PKC) modulators at each step. The results indicated that agonists of PKA enhanced both steps but that N-(2-[methylamino]ethyl-5-isoquinolinesulfonamide inhibited them. On the other hand, 1-oleyl-2-acetylglycerol and 12-O-tetradecanoylphorbol-13-acetate enhanced the commitment step but inhibited that of phenotypic expression. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited the commitment step and enhanced that of phenotypic expression. These results indicate that PKA acts as a positive regulatory signal and that PKC has a dual role in the process of HL-60 cell differentiation, i.e., as a positive regulatory signal in the commitment step and as a negative one in the phenotypic expression step. Recently, we have also shown that in K-562 cell differentiation into erythroid lineage, PKA may serve as a negative regulatory signal in both steps; however, PKC may act dually, namely as a negative regulatory signal in the commitment step and as a positive one in the phenotypic expression step.(ABSTRACT TRUNCATED AT 250 WORDS)     

A single cell approach to problems of cell lineage and commitment during embryogenesis of Drosophila melanogaster

The mechanisms leading to the commitment of a cell to a particular fate or to restrictions in its developmental potencies represent a problem of central importance in developmental biology. Both at the genetic and at the molecular level, studies addressing this topic using the fruitfly Drosophila melanogaster have advanced substantially, whereas, at the cellular level, experimental techniques have been most successfully applied to organisms composed of relatively large and accessible cells. The combined application of the different approaches to one system should improve our understanding of the process of commitment as a whole. Recently, a method has been devised to study cell lineage in Drosophila embryos at the single cell level. This method has been used to analyse the lineages, as well as the state of commitment of single cell progenitors from various ectodermal, mesodermal and endodermal anlagen and of the pole cells. The results obtained from a clonal analysis of wild-type larval structures are discussed in this review.     

miR-125 potentiates early neural specification of human embryonic stem cells

The role of microRNAs (miRNAs) as coordinators of stem cell fate has emerged over the last decade. We have used human embryonic stem cells to identify miRNAs involved in neural lineage commitment induced by the inhibition of TGFβ-like molecule-mediated pathways. Among several candidate miRNAs expressed in the fetal brain, the two isoforms of miR-125 alone were detected in a time window compatible with a role in neural commitment in vitro. Functional analysis indicated that miR-125 isoforms were actively involved in the promotion of pluripotent cell conversion into SOX1-positive neural precursors. miR-125 promotes neural conversion by avoiding the persistence of non-differentiated stem cells and repressing alternative fate choices. This was associated with the regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage commitment. Activation of miR-125 was directly responsive to the levels of TGFβ-like molecules, placing miR-125 at the core of mechanisms that lead to the irreversible neural lineage commitment of pluripotent stem cells in response to external stimuli.     

Patterning during pupal commitment of the epidermis in the butterfly, Precis coenia: the role of intercellular communication

The commitment of cells to pupal development in the larvae of holometabolous insects can be prevented by treatment with juvenile hormone (JH) or a JH mimic during a critical period early in the last larval instar. By treating larvae of different ages with a JH mimic, pupal commitment of the epidermis of the butterfly, Precis coenia, was found to occur in a strict temporal and spatial progression, which was serially homologous and occurred independently in each segment. The mechanism underlying this sequence of pupal commitment was examined by cauterizing regions of the epidermis to observe the effects of local ablation on the pattern of pupal commitment revealed by treatment with the JH mimic. Cautery of the segmental site of origin of pupal commitment, the dorsal midline, suppressed pupal commitment in the rest of the operated segment, indicating that the midline has a special effect on commitment of the rest of the segment. Cautery off the midline produced asymmetries in the pattern of pupal commitment; when placed close to the midline, such cauteries prevented pupal commitment in the region "downstream" of the cautery, suggesting that a signal (diffusible or transducible) emanates from the midline. Finally, cautery of a circle around the midline inhibited pupal commitment only outside the circle, showing that cautery could act as a barrier to the passage of a signal coming from the midline. These results suggest that inductive as well as hormonal signals are involved in the regulation of pupal commitment in the epidermis of the lepidopteran, P. coenia.     

Women social justice scholars: risks and rewards of committing to anti-racism

This article draws from the experiences of women, located in different countries, whose scholarship expresses a commitment to anti-racism and social justice. What are the challenges they face? How do they negotiate multiple commitments? Anti-racism scholars are border crossers and ethical leaders with a deep sense of care. Their experiences suggest that one does not necessarily have to engage in activism ‘out there’. The very commitment to anti-racism, as a scholar, becomes a form of social justice work. The ability to have a transformative impact both inside and outside of the academe enriches their sense of fulfilment as scholars.     

脂肪细胞的发育分化

脂肪组织是人体重要的能量贮存器官,同时还是一个重要的内分泌器官。适量的脂肪组织为人体所必需,但过多或过少的脂肪组织都会引起代谢综合征。脂肪细胞起源于血管基质中多潜能干细胞,这类干细胞具有自我更新和多向分化的潜能,在合适的条件下不仅可以分化为脂肪细胞,还可分化为肌肉细胞、软骨细胞和成骨细胞等中胚层来源的细胞。从多潜能干细胞到脂肪细胞的发育阶段可被分为三个阶段：（1）多潜能干细胞;（2）前脂肪细胞;（3）脂肪细胞。目前本领域的研究集中在干细胞定向为前脂肪细胞的机理以及这些定向为前脂肪细胞的干细胞的来源。该文将对从多潜能干细胞发育分化为成熟脂肪细胞的过程进行详细的阐述。     

Ionic regulation of MEL cell commitment

A key event in the initiation of the dimethyl sulfoxide (DMSO)-induced program of murine erythroleukemia (MEL) cell differentiation is a rise in the level of cytoplasmic calcium ions. Our interest in the present study is whether other inducers of the terminal erythroid differentiation program also act via a calcium-dependent pathway. Inhibition of calcium transport has been found to prevent the induction of MEL cell commitment by DMSO, butyric acid (BA), or hypoxanthine (HX). Enhancement of the calcium flux rate with A23187 or elevation of cytoplasmic calcium levels with FCCP stimulates the kinetics of commitment in response to all three inducers. These results suggest that of the inducers we have tested (DMSO, BA, and HX), all three act to initiate commitment via a common mechanism which involves modulation of cytoplasmic calcium levels.     

Developmental program of murine erythroleukemia cells. Effect of the inhibition of protein synthesis

The relationship between protein synthesis and commitment to terminal erythroid differentiation by dimethylsulfoxide-treated murine erythroleukemia (MEL) cells has been studied. Treatment with cycloheximide blocks the commitment of MEL cells. The effects of cycloheximide are completely reversible, however. Treatment of MEL cells before commitment delays commitment for a period of time equal to the length of inhibitor treatment. Puromycin exerts a similar effect on the commitment of MEL cells. These results indicate that there is a continuous requirement for protein synthesis before the commitment event.