scholarly journals Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

2019 ◽  
Author(s):  
Elena Lopez-Jimenez ◽  
Julio Sainz de Aja ◽  
Claudio Badia-Careaga ◽  
Antonio Barral ◽  
Isabel Rollan ◽  
...  
Keyword(s):  
Binding Sites ◽  
Early Embryo ◽  
Lineage Specification ◽  
Pluripotent Cells ◽  
Mammalian Embryo ◽  
Hox Cluster ◽  
Pluripotency Factors ◽  
Transient Population ◽  
Early Mammalian Embryo ◽  
Early Phases

ABSTRACTPluripotent cells are a transient population present in the early mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while simultaneously suppressing lineage specification. Interestingly, these factors are not exclusive to uncommitted cells, but are also expressed during early phases of differentiation. However, their role in the transition from pluripotency to lineage specification is largely unknown. Using genetic models for controlled Oct4 or Nanog expression during postimplantation stages, we found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that the HoxB cluster is coordinately regulated in this way by OCT4 binding sites located at the 3’ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the pre-committed epiblast, but are also necessary for the proper deployment of subsequent developmental programs.

Generation of embryonic stem cells: limitations of and alternatives to inner cell mass harvest

2008 ◽  
Vol 24 (3-4) ◽  
pp. E4 ◽  
Author(s):  
Sunit Das ◽  
Michael Bonaguidi ◽  
Kenji Muro ◽  
John A. Kessler
Keyword(s):  
Nuclear Transfer ◽  
Inner Cell Mass ◽  
Es Cells ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Ethical Considerations ◽  
Pluripotent Cells ◽  
Mammalian Embryo ◽  
Induced Pluripotency ◽  
Early Mammalian Embryo

✓ Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of the early mammalian embryo. Because of their plasticity and potentially unlimited capacity for self-renewal, ES cells have generated tremendous interest both as models for developmental biology and as possible tools for regenerative medicine. This excitement has been attenuated, however, by scientific, political, and ethical considerations. In this article the authors describe somatic cell nuclear transfer and transcription-induced pluripotency, 2 techniques that have been used in attempts to circumvent the need to derive ES cells by the harvest of embryonic tissue.

scholarly journals Amino Acids and the Early Mammalian Embryo: Origin, Fate, Function and Life-Long Legacy

2021 ◽  
Vol 18 (18) ◽  
pp. 9874
Author(s):  
Henry J. Leese ◽  
Paul McKeegan ◽  
Roger G Sturmey
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Culture Media ◽  
Early Embryo ◽  
Amino Acid Derivative ◽  
Cellular Functions ◽  
Traditional Role ◽  
Mammalian Embryo ◽  
Early Mammalian Embryo ◽  
And Function

Amino acids are now recognised as having multiple cellular functions in addition to their traditional role as constituents of proteins. This is well-illustrated in the early mammalian embryo where amino acids are now known to be involved in intermediary metabolism, as energy substrates, in signal transduction, osmoregulation and as intermediaries in numerous pathways which involve nitrogen metabolism, e.g., the biosynthesis of purines, pyrimidines, creatine and glutathione. The amino acid derivative S-adenosylmethionine has emerged as a universal methylating agent with a fundamental role in epigenetic regulation. Amino acids are now added routinely to preimplantation embryo culture media. This review examines the routes by which amino acids are supplied to the early embryo, focusing on the role of the oviduct epithelium, followed by an outline of their general fate and function within the embryo. Functions specific to individual amino acids are then considered. The importance of amino acids during the preimplantation period for maternal health and that of the conceptus long term, which has come from the developmental origins of health and disease concept of David Barker, is discussed and the review concludes by considering the potential utility of amino acid profiles as diagnostic of embryo health.

Genetic Control of Early Cell Lineages in the Mammalian Embryo

2018 ◽  
Vol 52 (1) ◽  
pp. 185-201 ◽  
Author(s):  
Janet Rossant
Keyword(s):  
Stem Cells ◽  
Gene Editing ◽  
Embryonic Stem ◽  
Pluripotent Cells ◽  
Mammalian Embryo ◽  
Cell Lineages ◽  
Fertility Treatments ◽  
Early Mammalian Embryo ◽  
Uterine Environment

Establishing the different lineages of the early mammalian embryo takes place over several days and several rounds of cell divisions from the fertilized egg. The resulting blastocyst contains the pluripotent cells of the epiblast, from which embryonic stem cells can be derived, as well as the extraembryonic lineages required for a mammalian embryo to survive in the uterine environment. The dynamics of the cellular and genetic interactions controlling the initiation and maintenance of these lineages in the mouse embryo are increasingly well understood through application of the tools of single-cell genomics, gene editing, and in vivo imaging. Exploring the similarities and differences between mouse and human development will be essential for translation of these findings into new insights into human biology, derivation of stem cells, and improvements in fertility treatments.

scholarly journals Parallels between embryo and cancer cell metabolism

2013 ◽  
Vol 41 (2) ◽  
pp. 664-669 ◽  
Author(s):  
Danielle G. Smith ◽  
Roger G. Sturmey
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Metabolic Regulation ◽  
Cell Metabolism ◽  
Early Embryo ◽  
Mammalian Embryo ◽  
Metabolic Switch ◽  
Early Mammalian Embryo ◽  
Cancer Cell Metabolism ◽  
The Warburg Effect

A key characteristic of cancer cells is the ability to switch from a predominantly oxidative metabolism to glycolysis and the production of lactate even when oxygen is plentiful. This metabolic switch, known as the Warburg effect, was first described in the 1920s, and has fascinated and puzzled researchers ever since. However, a dramatic increase in glycolysis in the presence of oxygen is one of the hallmarks of the development of the early mammalian embryo; a metabolic switch with many parallels to the Warburg effect of cancers. The present review provides a brief overview of this and other similarities between the metabolism in tumours and early embryos and proposes whether knowledge of early embryo metabolism can help us to understand metabolic regulation in cancer cells.

scholarly journals Genomic insights into chromatin reprogramming to totipotency in embryos

2018 ◽  
Vol 218 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Sabrina Ladstätter ◽  
Kikuë Tachibana
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Epigenetic Reprogramming ◽  
Mammalian Embryo ◽  
Cell Fate Decisions ◽  
A Cell ◽  
Early Mouse ◽  
Chromatin Reprogramming

The early embryo is the natural prototype for the acquisition of totipotency, which is the potential of a cell to produce a whole organism. Generation of a totipotent embryo involves chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications. Understanding embryonic chromatin architecture and how this is related to the epigenome and transcriptome will provide invaluable insights into cell fate decisions. Recently emerging low-input genomic assays allow the exploration of regulatory networks in the sparsely available mammalian embryo. Thus, the field of developmental biology is transitioning from microscopy to genome-wide chromatin descriptions. Ultimately, the prototype becomes a unique model for studying fundamental principles of development, epigenetic reprogramming, and cellular plasticity. In this review, we discuss chromatin reprogramming in the early mouse embryo, focusing on DNA methylation, chromatin accessibility, and higher-order chromatin structure.

Ex Uno Plures: Molecular Designs for Embryonic Pluripotency

2015 ◽  
Vol 95 (1) ◽  
pp. 245-295 ◽  
Author(s):  
Kyle M. Loh ◽  
Bing Lim ◽  
Lay Teng Ang
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Cell Lines ◽  
Multilineage Differentiation ◽  
Pluripotent Cells ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Pluripotency Factors ◽  
Stem Cell Lines

Pluripotent cells in embryos are situated near the apex of the hierarchy of developmental potential. They are capable of generating all cell types of the mammalian body proper. Therefore, they are the exemplar of stem cells. In vivo, pluripotent cells exist transiently and become expended within a few days of their establishment. Yet, when explanted into artificial culture conditions, they can be indefinitely propagated in vitro as pluripotent stem cell lines. A host of transcription factors and regulatory genes are now known to underpin the pluripotent state. Nonetheless, how pluripotent cells are equipped with their vast multilineage differentiation potential remains elusive. Consensus holds that pluripotency transcription factors prevent differentiation by inhibiting the expression of differentiation genes. However, this does not explain the developmental potential of pluripotent cells. We have presented another emergent perspective, namely, that pluripotency factors function as lineage specifiers that enable pluripotent cells to differentiate into specific lineages, therefore endowing pluripotent cells with their multilineage potential. Here we provide a comprehensive overview of the developmental biology, transcription factors, and extrinsic signaling associated with pluripotent cells, and their accompanying subtypes, in vitro heterogeneity and chromatin states. Although much has been learned since the appreciation of mammalian pluripotency in the 1950s and the derivation of embryonic stem cell lines in 1981, we will specifically emphasize what currently remains unclear. However, the view that pluripotency factors capacitate differentiation, recently corroborated by experimental evidence, might perhaps address the long-standing question of how pluripotent cells are endowed with their multilineage differentiation potential.

259. Pluripotency genes in a marsupial, the tammar wallaby

2008 ◽  
Vol 20 (9) ◽  
pp. 59
Author(s):  
S. Frankenberg ◽  
A. J. Pask ◽  
M. B. Renfree
Keyword(s):  
Expression Profiles ◽  
Genomic Analysis ◽  
Tammar Wallaby ◽  
Early Embryo ◽  
Lineage Specification ◽  
Signalling Molecules ◽  
Early Embryos ◽  
Genes Encoding ◽  
Morphological Differences ◽  
Pluripotency Genes

Markers of pluripotency and early differentiation in the early embryo have been extensively characterised in eutherian species, most notably the mouse. By comparison, mechanisms controlling pluripotency and early lineage specification have received surprisingly little attention in marsupials, which represent the second major infraclass of mammals. Early marsupial embryogenesis exhibits overt morphological differences to that of eutherians, however the underlying developmental mechanisms may be conserved. In order to characterise early marsupial development at the molecular level, we have identified, cloned and analysed expression of orthologueues of several eutherian genes encoding transcription factors and signalling molecules involved in regulating pluripotency and early lineage specification. These genes include POU5F1 (OCT4), SOX2, NANOG, FGF4, FGFR2, CDX2, EOMES, TEAD4, GATA6 and KITL and are all expressed at early stages of development in the tammar. In addition, we have identified and cloned tammar POU2, which has orthologueues in non-mammalian vertebrates. POU2 is a paralogue of POU5F1 – a master regulator of pluripotency in eutherians. Genomic analysis indicates that POU5F1 arose via gene duplication of POU2 before the monotreme-therian divergence. Both genes have persisted in marsupials and monotremes, while POU2 was lost early during eutherian evolution. Similar expression profiles of tammar POU5F1 and POU2 in early embryos and gonadal tissues suggest possible overlapping roles in the maintenance of pluripotency.

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