• Stem and progenitor cell populations are often heterogeneous, which may reflect stem cell subsets that express subtly different properties, including different propensities for lineage selection upon differentiation, yet remain able to interconvert. (lu.se)
  • A key challenge is to understand how state, but must also afford flexibility in cell-fate choice to permit the different cell-fate options confronting stem and progenitor cell-type diversification and differentiation in response to cells are selected and coordinated such that adoption of a given intrinsic cues or extrinsic signals. (lu.se)
  • Evidence the fate of stem cells has broad ramifications for biomedical suggests that during development or differentiation, cells make science from elucidating the causes of cancer to the use of very precise transitions between apparently stable ``network stem cells in regenerative medicine. (lu.se)
  • 1 Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan. (jci.org)
  • To establish protocols for the safe and efficient differentiation of healthy cells for therapies, we must develop a better understanding of the dynamic continuum of metabolic states that span pluripotency and differentiation, and how to influence them. (conditionmed.org)
  • Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)
  • Accordingly, scientists have developed protocols for the expansion, genetic modification and differentiation of stem cells to NK cells. (molcells.org)
  • Dazl can regulate the expression, transport and localization of target mRNAs of proteins which control the differentiation, growth and maturation of germ cells. (ijbs.com)
  • The AF form of SALSA had a more intact structure and contained peptides from the zona pellucida domain, which is involved in cell differentiation and oligomerization. (researchgate.net)
  • Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues. (mpi-cbg.de)
  • Patterns are ubiquitous in living systems and underlie the dynamic organization of cells, tissues, and embryos. (mpi-cbg.de)
  • Some of these concerns, such as ensuring the welfare of research animals and obtaining appropriate consent for the use of human tissues, also apply to many other areas of research, but may require special consideration for research with human neural organoids, cell transplants, and chimeras. (nationalacademies.org)
  • Given the complexity of the human brain and the particularly human nature of many key symptoms of these disorders, especially psychiatric disorders, animal and cell culture models of the types currently used to investigate diseases of other organs and tissues are valuable but inadequate. (nationalacademies.org)
  • Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking 1 , 2 . (nature.com)
  • Much of this process relies on the morphogenesis of the extra-embryonic tissues and the effect this has on the organization of embryonic cells. (nature.com)
  • Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
  • In reality, gene somatic cells to a pluripotent cell state by a handful of transcrip- expression is graded, making the potential gene expression tion factors (Takahashi and Yamanaka, 2006). (lu.se)
  • … "human clone" means an embryo that, as a result of the manipulation of human reproductive material or an in vitro embryo, contains a diploid set of chromosomes obtained from a single - living or deceased - human being, fetus, or embryo. (hinxtongroup.org)
  • We discuss what is known about the distinct metabolic states captured in vitro by the 2-cell-like, naïve, blastocyst-like, formative, and primed states of pluripotency. (conditionmed.org)
  • 2019). Akin to the dynamic nutrient requirements of the developing embryo, discrete in vitro cell states have distinct metabolic profiles (Zhou et al. (conditionmed.org)
  • It is only through understanding embryonic metabolism and development that we can derive and maintain different in vitro stem cell states for disease modeling and therapies. (conditionmed.org)
  • In 1-cell and 2-cell embryos Dnmt1s is derived from the oocyte, whereas from the 2-cell stage onward the embryo starts to synthesize its own Dnmt1s 8 . (nature.com)
  • Monkeys have served as one of the most valuable models for understanding DNA methylation dynamics during early embryogenesis in human due to their similarities in genetics and early embryonic development 17 , 18 . (nature.com)
  • Furthermore, due to ethical and legal concerns, very limited techniques can be applied to human embryos to validate some of significant conclusions drawn from descriptive studies regarding human embryonic development. (nature.com)
  • Acquisition of limb-forming ability by discrete regions of the lateral plate of the chick embryo is thought to depend on a signaling cascade moving sequentially from the area of Hensen's node to the somitic mesoderm, the intermediate mesoderm, and then to the prospective limb-forming regions of the lateral plate (Step. (shengsci.com)
  • However, robust and large-scale genome-wide reprogramming of DNA methylome occurs during two critical developmental processes: (1) development of primordial germ cells and (2) pre-implantation embryogenesis. (nature.com)
  • To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology. (frontiersin.org)
  • These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days after fertilization (Carnegie stage 6a). (nature.com)
  • and (3) evidence of developmental dynamism relating to ability to progress, in a structurally organized manner, through morphologically characterized developmental milestones of the early post-implantation human embryo following initial aggregate formation 3 . (nature.com)
  • DAZ family proteins are located in the nucleus and/or in the cytoplasm of male and female germ cells at different developmental stages throughout the gametogenesis. (ijbs.com)
  • Among PSCs, the donors available for induced pluripotent stem cells (iPSCs) are greatest, providing a potentially universal cell source for all types of cell therapies including cancer immunotherapies using natural killer (NK cells). (molcells.org)
  • In terminally differentiated cell fate is coupled to appropriate regulation of the alternative cells, transcriptional networks must be stable and irreversible, pathways. (lu.se)
  • We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. (stanford.edu)
  • Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions) 4 . (nature.com)
  • There already exist several protocols to genetically modify and differentiate iPSCs into NK cells, and each has its own advantages with regards to immunotherapies. (molcells.org)
  • We discuss these properties with examples both from the hematopoietic and embryonic stem cell (ESC) systems. (lu.se)
  • We are studying the role that normal chromatin structure plays in gene regulation in hematopoietic cells and how its disruption leads to altered development and cancer. (stanford.edu)
  • This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
  • Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. (shengsci.com)
  • In mice, nuage that is prominent in postnatal male germ cells is also called intermitochondrial cement or chromatoid bodies. (shengsci.com)
  • DAZ family proteins are found almost exclusively in germ cells in distant animal species. (ijbs.com)
  • Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. (ijbs.com)
  • … "embryo" means a human organism during the first 56 days of its development following fertilization or creation, excluding any time during which its development has been suspended, and includes any cell derived from such an organism that is used for the purpose of creating a human being. (hinxtongroup.org)
  • We therefore decided to investigate comprehensively the global and high-resolution DNA methylation dynamics during early development of a non-human primate (rhesus monkey, Macaca mulatta ). (nature.com)
  • As explained in Chapter 2 , human neural organoids, transplants, and chimeras provide new models for such conditions and may lead to new knowledge about brain development and function, the discovery of disease mechanisms, new therapeutic targets, and better screening of potential new treatments. (nationalacademies.org)
  • Here, we consider the metabolism of the early embryo through development, and look at the nutrient milieu within the developing stem cell niche. (conditionmed.org)
  • 2020). This places metabolism at the forefront of development and cell state decisions. (conditionmed.org)
  • The developing embryo, from which pluripotent stem cells originate, undergoes a series of dynamic metabolic transitions synchronized to its molecular development. (conditionmed.org)
  • The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation 1 . (nature.com)
  • This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development. (nature.com)
  • Implantation of the human embryo leads to a number of changes in organization that are essential for gastrulation and future development 1 . (nature.com)
  • These data provide insight into epigenetic errors that may be associated with the poor development of embryos generated from immature spermatozoa. (shengsci.com)
  • In studies initially focused on roles of nonmuscle myosin IIA (NMIIA) in the developing mouse epidermis, we have discovered that a previously described cytokeratin 5 (K5)-Cre gene construct is expressed in early embryo development. (shengsci.com)
  • BACKGROUND: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. (atlas-d2k.org)
  • The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation. (atlas-d2k.org)
  • These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. (nature.com)
  • Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. (nature.com)
  • Although it is possible to culture structures derived from human blastocysts ex vivo, these cultures do not recapitulate the events and structural organization of the in vivo embryos 6 ( Supplementary Information ). (nature.com)
  • Similarly, GATA-1 has been shown to induce lineage switching expression values even if, for simplicity, we assume only ``on'' of committed cells in hematopoiesis, first in cell lines (Kulessa and ``off'' states for each gene. (lu.se)
  • In this review, we examine the manufacturing and gene engineering of NK cells generated from iPSCs (iPS-NK) for ACT. (molcells.org)
  • Deletion of DAZ gene is the most common causes of infertility in humans. (ijbs.com)
  • Research involving human neural organoids, transplants, and chimeras has an ultimate goal of preventing and treating the great suffering caused by serious neurological and psychiatric conditions for which no effective treatment is available. (nationalacademies.org)
  • One such concern is the possibility of altering the capacities or consciousness of a research animal in ways that may blur the lines between human beings and nonhuman animals. (nationalacademies.org)
  • A main justification for carrying out research, both basic and translational, with human neural organoids, transplants, and chimeras is that it will help in the discovery of new ways to understand and treat neurological and psychiatric disorders, which, as discussed previously, cause immense suffering and for which treatments are ineffective or lacking. (nationalacademies.org)
  • In Enhancing Evolution, leading bioethicist John Harris dismantles objections to genetic engineering, stem-cell research, designer babies, and cloning and makes an ethical case for biotechnology that is both forthright and rigorous. (philpapers.org)
  • International bi-monthly journal of cell signaling, tissue protection, and translational research. (conditionmed.org)
  • The discovery of human pluripotent stem cells (PSCs) at the turn of the century opened the door to a new generation of regenerative medicine research. (molcells.org)
  • Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. (shengsci.com)
  • We explore the recently described metabolic surge event that occurs as pluripotency is lost and stem cells commit to differentiate. (conditionmed.org)
  • 2008). Historically, this concept is highlighted by the experi- factors are key intrinsic regulators of these fate decisions and mental phenomenon of lineage reprogramming, for example, that fate choice involves modulating networks of transcription by the conversion of fibroblasts to muscles cells following trans- factors. (lu.se)
  • In cultured primary fibroblasts and cancer cells, the chemotherapeutic drug doxorubicin causes mtDNA damage and release, which leads to cGAS STING dependent ISG activation. (regenerativemedicine.net)
  • Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. (nature.com)
  • Although the genome-wide DNA demethylation is believed to be a hallmark of mammalian embryogenesis, previous study also indicated that the somatic form of dnmt1 ( dnmt1s ) is actually expressed at each stage of pre-implantation embryos and plays a role in the maintenance of DNA imprinting 8 . (nature.com)
  • explosion further, consider that a fictitious small genome with 2002) More recently and more dramatically, the potential for 260 genes would host the same number of combinations as cell state conversions is exemplified by the reprogramming of the number of atoms in the visible universe! (lu.se)
  • Genomes from elongated spermatids exhibited an intermediate level of DNA methylation, between those of round spermatids and mature spermatozoa, suggesting that the male germ cell acquires the ability to maintain its undermethylated state in the paternal zygotic genome during this phase of spermiogenesis. (shengsci.com)
  • Ethical issues common to human neural organoids, transplants, and chimeras include (1) the ethical value of relieving human suffering and disease, (2) concerns about encroachment on divine roles, and (3) ethical issues related to human donors of biological materials. (nationalacademies.org)
  • 3) We are defining the properties of cancer stem cells that initiate and sustain the unique disease features of acute leukemias through the use of various adoptive animal models. (stanford.edu)
  • Understanding cell-fate decisions in stem cell populations is a major goal of modern biology. (lu.se)
  • Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. (atlas-d2k.org)
  • Chapter 2 presents the science behind these models and describes the challenges of measuring and monitoring such characteristics and capacities in human neural organoids, transplants, and chimeras. (nationalacademies.org)
  • neural organoids, transplants, and chimeras, and then at issues specific to human neural transplants and chimeras or to neural organoids. (nationalacademies.org)
  • The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. (atlas-d2k.org)
  • He probes the male mouse's reaction to chemical signals from female mice to advance understanding of pattern recognition and learning in the much more complex human brain. (vetscite.org)
  • These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. (bvsalud.org)
  • Our project focuses on characterizing and optimizing this approach to improve tubular maturation and cellular function and generating reporter lines for the isolation of specific cell types. (atlas-d2k.org)
  • In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. (frontiersin.org)
  • In the mouse, a transporting epithelium is established around the 8-16-cell stage through a process known as compaction where cell definition is lost and the outer cells of the embryo form tight junctions, giving rise to the blastocyst. (conditionmed.org)
  • The blastocyst comprises the inner cell mass (ICM), which gives rise to the three primary germ layers and consequently the fetus, and the trophectoderm (TE), which gives rise to the extraembryonic and placental tissue. (conditionmed.org)
  • XI - embryonic stem cells: embryonic cells that are capable of modifying the cells of any organism tissue. (hinxtongroup.org)
  • On the other hand, a chimera is defined as an organism in which cells from two or more different organisms have contributed. (frontiersin.org)
  • In the long term, human kidney tissue generated in this way may be used for drug screening, tissue regeneration or cell therapy. (atlas-d2k.org)
  • The nature of the stem cell substates and their relationship to commitment to differ- entiate and lineage selection can be elucidated in terms of a landscape picture in which stable states can be defined mathematically as attractors. (lu.se)
  • The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. (atlas-d2k.org)
  • Promoters of genes associated with oxidative phosphorylation are preferentially remethylated at the 8-cell stage, suggesting that this mode of energy metabolism may not be favored. (nature.com)
  • DAZ (Deleted in Azoospermia) family genes are important fertility factors in many animals including humans. (ijbs.com)
  • In human, an array of four DAZ genes ( DAZ 1-4) is located in two clusters on the Y chromosome and mutations of these genes cause severe oligospermia or azospermia [ 1 ]. (ijbs.com)
  • The biological properties and clinical potential of stem cells elicit that are generated must not be unduly sensitive to small fluctu- continued scientific, commercial, and public interest. (lu.se)
  • In this review, we summarize the history of interspecies chimerism in various animal models to find hints for BC application and describe the challenges and prospects of utilizing BC for human organ generation. (frontiersin.org)
  • Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs) 3 . (nature.com)
  • However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. (atlas-d2k.org)
  • On the other hand, other ligands, such as HLA, bind to inhibitory receptors NKG2A and killer immunoglobulin-like receptors (KIR) to inhibit NK cells, providing a form of protection for self-cells from innate immunity. (molcells.org)
  • Cliff and Dalton, 2017), with nutrients capable of inducing and maintaining alternate cell states (Shyh-Chang et al. (conditionmed.org)
  • To varying degrees, these fates also extend to the Such state stability is required in stem and progenitor cells to immediate progeny of stem cells, known as progenitor or support self-renewal and maintenance of the uncommitted transit-amplifying cells. (lu.se)
  • The germ-line cells of many animals possess a characteristic cytoplasmic structure termed nuage or germinal granules. (shengsci.com)
  • They found the compounds activate nerve cells in the male mouse's nose with unprecedented effectiveness. (vetscite.org)
  • Ancestral Boule is present from sea anemones through humans and Dazl is conserved among vertebrates. (ijbs.com)
  • Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. (atlas-d2k.org)
  • Thousands of copies of the circular mtDNA are present in most cell types that are packaged by TFAM into higher-order structures called nucleoids1. (regenerativemedicine.net)
  • In addition, mtDNA stress in TFAM-deficient mouse melanoma cells produces tumours that are more resistant to doxorubicin in vivo. (regenerativemedicine.net)
  • However, though BC is emerging as a potential organ transplant option, challenges regarding organ size scalability, immune system incompatibilities, long-term maintenance, potential evolutionary distance, or unveiled mechanisms between donor and host cells remain. (frontiersin.org)
  • Up to the 2-cell embryo, blastomeres remain totipotent (Garner and McLaren, 1974). (conditionmed.org)
  • However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. (bvsalud.org)
  • We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). (bvsalud.org)
  • Adoptive cell transfer (ACT) is the latest arsenal in the battle against cancer. (molcells.org)
  • We apply our method to four 2D and seven 3D benchmark datasets, showing that we either match or outperform existing state-of-the-art methods. (mpi-cbg.de)