The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.
- Keywords
- LSD1, Myh4, Olfr, TPR, gene expression, myogenic differentiation, nucleoporin, translocated promoter region,
- MeSH
- Cell Differentiation MeSH
- Cell Line MeSH
- Gene Expression MeSH
- Nuclear Pore Complex Proteins metabolism MeSH
- Muscle Fibers, Skeletal * cytology metabolism MeSH
- Myoblasts, Skeletal * cytology metabolism MeSH
- Mice MeSH
- Proto-Oncogene Proteins metabolism MeSH
- Gene Expression Regulation MeSH
- Myosin Heavy Chains metabolism MeSH
- Muscle Development MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Nuclear Pore Complex Proteins MeSH
- MYH4 protein, mouse MeSH Browser
- Proto-Oncogene Proteins MeSH
- Myosin Heavy Chains MeSH
- TPR protein, mouse MeSH Browser
Considerable evidence indicates that the first phenotypical diversification of embryonic cells during mammalian preimplantation development is achieved in two successive steps: (i) generation of cell asymmetry and (ii) unequal cell division. This paper shows that ultrastructural signs of blastomere surface regionalization in human preimplantation embryos are evident as early as the 2-cell stage when modifications of the plasma membrane (loss of microvilli and endocytotic activity, formation of cell junctions) are induced in places of blastomere contact. The capacity of the plasma membrane to undergo these cell-contact-dependent changes precedes any detectable activity of the embryonic genome. The area of the modified plasma membrane shows a continuous increase during the first three cleavage stages. The progression of these membrane modifications is the same in embryos that have properly enhanced their transcriptional activity at the 8-cell stage and in those that have not. In spite of the failure of this early-cleavage-progressed-cleavage transition of gene activity, the formation of zonula adherens and gap junctions goes on apparently normally in the respective embryos and morphologically distinct inner cell mass and trophectoderm cell lineages are subsequently segregated in 16-cell morulae. However, tight junctions do not develop under these conditions. The occurrence of the progressed-cleavage pattern of gene activity in the majority of embryonic cells is a necessary prerequisite for the appearance of the blastocyst cavity. Thus, oocyte-coded message is apparently involved in the control of relatively late stages of human preimplantation development including the differentiation of the first two embryonic tissues, but the embryonic genome is required for the full achievement of this early differentiative event.
- MeSH
- Blastomeres physiology MeSH
- Cell Differentiation * MeSH
- Cell Membrane physiology MeSH
- Embryonic Development MeSH
- Humans MeSH
- Oocytes physiology MeSH
- Gene Expression Regulation MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Histochemical differentiation of 12 skeletal muscles with a different fibre type composition was studied in miniature pigs from 80 d of gestation to 1 year of age. Two fetal myofibre types were distinguished at 100 d of gestation by the mATPase reaction after acid preincubation. The staining for oxidative enzyme activities showed no conspicuous differences between fibres up to the 6th day after birth. Starting from this age it was possible to distinguish 3 fibre categories: SO (slow-twitch oxidative); FOG (fast-twitch oxidative-glycolytic); and FG (fast-twitch glycolytic). A characteristic cluster distribution of the 3 fibre types was observed in all studied muscles with the exception of the masseter muscle which consisted only of the type SO and FOG fibres with a mosaic arrangement. The frequencies of both SO and FG fibre types increased and the proportion of type FOG fibres decreased during the postnatal period. These changes could be explained by developmental transformations among the individual fibre types. The type FOG fibres converted preferably to the fibre type (SO or FG) that prevailed in the muscles of adult animals.
- MeSH
- Adenosine Triphosphatases analysis MeSH
- Cell Differentiation MeSH
- Gestational Age MeSH
- Histocytochemistry MeSH
- Muscle Fibers, Skeletal cytology MeSH
- Muscle, Skeletal embryology growth & development MeSH
- Swine, Miniature growth & development MeSH
- Swine MeSH
- Aging MeSH
- Muscle Fibers, Slow-Twitch cytology enzymology MeSH
- Muscle Fibers, Fast-Twitch cytology enzymology MeSH
- Muscle Development * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenosine Triphosphatases MeSH
Successful specification of the two mouse blastocyst inner cell mass (ICM) lineages (the primitive endoderm (PrE) and epiblast) is a prerequisite for continued development and requires active fibroblast growth factor 4 (FGF4) signaling. Previously, we identified a role for p38 mitogen-activated protein kinases (p38-MAPKs) during PrE differentiation, but the underlying mechanisms have remained unresolved. Here, we report an early blastocyst window of p38-MAPK activity that is required to regulate ribosome-related gene expression, rRNA precursor processing, polysome formation and protein translation. We show that p38-MAPK inhibition-induced PrE phenotypes can be partially rescued by activating the translational regulator mTOR. However, similar PrE phenotypes associated with extracellular signal-regulated kinase (ERK) pathway inhibition targeting active FGF4 signaling are not affected by mTOR activation. These data indicate a specific role for p38-MAPKs in providing a permissive translational environment during mouse blastocyst PrE differentiation that is distinct from classically reported FGF4-based mechanisms.
- MeSH
- Blastocyst physiology MeSH
- Cell Differentiation MeSH
- Cell Lineage MeSH
- DNA-Binding Proteins physiology MeSH
- Embryonic Development MeSH
- Endoderm cytology MeSH
- p38 Mitogen-Activated Protein Kinases antagonists & inhibitors physiology MeSH
- Mice MeSH
- RNA-Binding Proteins physiology MeSH
- Protein Biosynthesis * MeSH
- TOR Serine-Threonine Kinases physiology MeSH
- Transcription Factors physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Binding Proteins MeSH
- p38 Mitogen-Activated Protein Kinases MeSH
- mTOR protein, mouse MeSH Browser
- Mybbp1a protein, mouse MeSH Browser
- RNA-Binding Proteins MeSH
- TOR Serine-Threonine Kinases MeSH
- Transcription Factors MeSH
During mouse preimplantation embryo development, the classically described second cell-fate decision involves the specification and segregation, in blastocyst inner cell mass (ICM), of primitive endoderm (PrE) from pluripotent epiblast (EPI). The active role of fibroblast growth factor (Fgf) signalling during PrE differentiation, particularly in the context of Erk1/2 pathway activation, is well described. However, we report that p38 family mitogen-activated protein kinases (namely p38α/Mapk14 and p38β/Mapk11; referred to as p38-Mapk14/11) also participate in PrE formation. Specifically, functional p38-Mapk14/11 are required, during early-blastocyst maturation, to assist uncommitted ICM cells, expressing both EPI and earlier PrE markers, to fully commit to PrE differentiation. Moreover, functional activation of p38-Mapk14/11 is, as reported for Erk1/2, under the control of Fgf-receptor signalling, plus active Tak1 kinase (involved in non-canonical bone morphogenetic protein (Bmp)-receptor-mediated PrE differentiation). However, we demonstrate that the critical window of p38-Mapk14/11 activation precedes the E3.75 timepoint (defined by the initiation of the classical 'salt and pepper' expression pattern of mutually exclusive EPI and PrE markers), whereas appropriate lineage maturation is still achievable when Erk1/2 activity (via Mek1/2 inhibition) is limited to a period after E3.75. We propose that active p38-Mapk14/11 act as enablers, and Erk1/2 as drivers, of PrE differentiation during ICM lineage specification and segregation.
- Keywords
- cell signalling, cell-fate, mitogen-activated protein kinase, p38α/p38β Mapk14/Mapk11, preimplantation mouse embryo, primitive endoderm,
- MeSH
- Blastocyst physiology MeSH
- Cell Differentiation MeSH
- Embryonic Development * MeSH
- Endoderm embryology MeSH
- Fibroblast Growth Factors metabolism MeSH
- RNA, Messenger metabolism MeSH
- Mitogen-Activated Protein Kinase 11 metabolism MeSH
- Mitogen-Activated Protein Kinase 14 metabolism MeSH
- Mice MeSH
- Signal Transduction MeSH
- Germ Layers physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fibroblast Growth Factors MeSH
- RNA, Messenger MeSH
- Mitogen-Activated Protein Kinase 11 MeSH
- Mitogen-Activated Protein Kinase 14 MeSH
The molecular machinery of endoplasmic reticulum (ER) integrates various intracellular and extracellular cues to maintain homeostasis in diverse physiological or pathological scenarios. ER stress and the unfolded protein response (UPR) have been found to mediate molecular and biochemical mechanisms that affect cell proliferation, differentiation, and apoptosis. Although a number of reviews on the ER stress response have been published, comprehensive reviews that broadly summarize ER physiology in the context of pluripotency, embryonic development, and tissue homeostasis are lacking. This review complements the current ER literature and provides a summary of the important findings on the role of the ER stress and UPR in embryonic development and pluripotent stem cells.
- Keywords
- Development, Embryonic stem cells, Endoplasmic reticulum stress, Pluripotency, Unfolded protein response,
- MeSH
- Cell Differentiation * MeSH
- Embryonic Development * MeSH
- Homeostasis MeSH
- Humans MeSH
- Pluripotent Stem Cells cytology metabolism MeSH
- Endoplasmic Reticulum Stress * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Leukocyte membrane markers have been examined within cryostat sections and cell suspensions of human fetuses aged between 4 and 18 weeks of gestation using a panel of monoclonal antibodies. The HLA-DR molecule was present on a population of erythroid cells and macrophages in liver sinuses at 34 days and periarteriolar splenic macrophages at 60 days of gestation. CD5, CD15 and CD45 antigens were detected at 6 weeks of gestation, whereas CD4, CD8, CD10, CD11c, CD14 and IgM were not expressed at this stage. These findings and ultrastructural examination of embryonic liver confirm early differentiation of macrophages in the pre-lymphatic developmental period.
- MeSH
- Antigens, Differentiation analysis biosynthesis MeSH
- Embryonic and Fetal Development immunology MeSH
- Gestational Age MeSH
- HLA-DR Antigens analysis biosynthesis MeSH
- Liver embryology immunology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens, Differentiation MeSH
- HLA-DR Antigens MeSH
Differentiation during hematopoiesis leads to the generation of many cell types with specific functions. At various stages of maturation, the cells may change pathologically, leading to diseases including acute leukemias (ALs). Expression levels of regulatory molecules (such as the IKZF, GATA, HOX, FOX, NOTCH and CEBP families, as well as SPI-1/PU1 and PAX5) and lineage-specific molecules (including CD2, CD14, CD79A, and BLNK) may be compared between pathological and physiological cells. Although the key steps of differentiation are known, the available databases focus mainly on fully differentiated cells as a reference. Precursor cells may be a more appropriate reference point for diseases that evolve at immature stages. Therefore, we developed a quantitative real-time polymerase chain reaction (qPCR) array to investigate 90 genes that are characteristic of the lymphoid or myeloid lineages and/or are thought to be involved in their regulation. Using this array, sorted cells of granulocytic, monocytic, T and B lineages were analyzed. For each of these lineages, 3-5 differentiation stages were selected (17 stages total), and cells were sorted from 3 different donors per stage. The qPCR results were compared to similarly processed AL cells of lymphoblastic (n=18) or myeloid (n=6) origins and biphenotypic AL cells of B cell origin with myeloid involvement (n=5). Molecules characteristic of each lineage were found. In addition, cells of a newly discovered switching lymphoblastic AL (swALL) were sorted at various phases during the supposed transdifferentiation from an immature B cell to a monocytic phenotype. As demonstrated previously, gene expression changed along with the immunophenotype. The qPCR data are publicly available in the LeukoStage Database in which gene expression in malignant and non-malignant cells of different lineages can be explored graphically and differentially expressed genes can be identified. In addition, the LeukoStage Database can aid the functional analyses of next-generation sequencing data.
- Keywords
- Acute leukemia, B and T lymphocytes, Differentiation plasticity, Gene expression, Hematopoiesis, Lineage promiscuity,
- MeSH
- Leukemia, Biphenotypic, Acute genetics immunology pathology MeSH
- B-Lymphocytes immunology pathology MeSH
- Cell Differentiation genetics MeSH
- Cell Lineage genetics MeSH
- Tissue Array Analysis MeSH
- Hematopoiesis genetics MeSH
- Immunophenotyping MeSH
- Humans MeSH
- Neoplasm Proteins biosynthesis MeSH
- Gene Expression Regulation, Leukemic MeSH
- T-Lymphocytes immunology pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Neoplasm Proteins MeSH
Yeasts, historically considered to be single-cell organisms, are able to activate different differentiation processes. Individual yeast cells can change their life-styles by processes of phenotypic switching such as the switch from yeast-shaped cells to filamentous cells (pseudohyphae or true hyphae) and the transition among opaque, white and gray cell-types. Yeasts can also create organized multicellular structures such as colonies and biofilms, and the latter are often observed as contaminants on surfaces in industry and medical care and are formed during infections of the human body. Multicellular structures are formed mostly of stationary-phase or slow-growing cells that diversify into specific cell subpopulations that have unique metabolic properties and can fulfill specific tasks. In addition to the development of multiple protective mechanisms, processes of metabolic reprogramming that reflect a changed environment help differentiated individual cells and/or community cell constituents to survive harmful environmental attacks and/or to escape the host immune system. This review aims to provide an overview of differentiation processes so far identified in individual yeast cells as well as in multicellular communities of yeast pathogens of the Candida and Cryptococcus spp. and the Candida albicans close relative, Saccharomyces cerevisiae. Molecular mechanisms and extracellular signals potentially involved in differentiation processes are also briefly mentioned.
- Keywords
- Biofilms and colonies, Candida, Cell differentiation, Cryptococcus and Saccharomyces spp., Pathogenic yeasts, Phenotypic switching,
- MeSH
- Biofilms MeSH
- Cell Differentiation * MeSH
- Phenotype MeSH
- Yeasts cytology physiology ultrastructure MeSH
- Signal Transduction MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
