scholarly journals The multi-faceted role of Gata3 in developmental haematopoiesis

Open Biology ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 180152 ◽  
Author(s):  
Nada Zaidan ◽  
Katrin Ottersbach
Keyword(s):  
Cell Fate ◽  
Complex Nature ◽  
Haematopoietic Stem Cells ◽  
Cell Cycle Genes ◽  
Cell Lineages ◽  
Early Embryonic Lethality ◽  
Determining Factors ◽  
Stem And Progenitor Cells ◽  
Cancer Types

The transcription factor Gata3 is crucial for the development of several tissues and cell lineages both during development as well as postnatally. This importance is apparent from the early embryonic lethality following germline Gata3 deletion, with embryos displaying a number of phenotypes, and from the fact that Gata3 has been implicated in several cancer types. It often acts at the level of stem and progenitor cells in which it controls the expression of key lineage-determining factors as well as cell cycle genes, thus being one of the main drivers of cell fate choice and tissue morphogenesis. Gata3 is involved at various stages of haematopoiesis both in the adult as well as during development. This review summarizes the various contributions of Gata3 to haematopoiesis with a particular focus on the emergence of the first haematopoietic stem cells in the embryo—a process that appears to be influenced by Gata3 at various levels, thus highlighting the complex nature of Gata3 action.

scholarly journals Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1591 ◽  
Author(s):  
Laura Reiche ◽  
Patrick Küry ◽  
Peter Göttle
Keyword(s):  
Down Syndrome ◽  
White Matter ◽  
Cell Fate ◽  
Neuronal Development ◽  
Demyelinating Diseases ◽  
Therapeutic Interventions ◽  
Cell Lineages ◽  
Cns Malformations ◽  
Current Experience

Down syndrome (DS), or trisomy 21, is the most prevalent chromosomal anomaly accounting for cognitive impairment and intellectual disability (ID). Neuropathological changes of DS brains are characterized by a reduction in the number of neurons and oligodendrocytes, accompanied by hypomyelination and astrogliosis. Recent studies mainly focused on neuronal development in DS, but underestimated the role of glial cells as pathogenic players. Aberrant or impaired differentiation within the oligodendroglial lineage and altered white matter functionality are thought to contribute to central nervous system (CNS) malformations. Given that white matter, comprised of oligodendrocytes and their myelin sheaths, is vital for higher brain function, gathering knowledge about pathways and modulators challenging oligodendrogenesis and cell lineages within DS is essential. This review article discusses to what degree DS-related effects on oligodendroglial cells have been described and presents collected evidence regarding induced cell-fate switches, thereby resulting in an enhanced generation of astrocytes. Moreover, alterations in white matter formation observed in mouse and human post-mortem brains are described. Finally, the rationale for a better understanding of pathways and modulators responsible for the glial cell imbalance as a possible source for future therapeutic interventions is given based on current experience on pro-oligodendroglial treatment approaches developed for demyelinating diseases, such as multiple sclerosis.

The Ordered Expression of Transcription Factors Directs Hierarchical Lineage Specification of Eosinophils, Basophils and Mast Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 224-224
Author(s):  
Hiromi Iwasaki ◽  
Yojiro Arinobu ◽  
Shin-ichi Mizuno ◽  
Hirokazu Shigematsu ◽  
Kiyoshi Takatsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Mast Cell ◽  
Cell Fate ◽  
Gene Expression Analysis ◽  
Lineage Specification ◽  
Retroviral Transduction ◽  
Cell Lineages ◽  
Stem And Progenitor Cells ◽  
Eosinophil Colonies

Abstract Here we show that eosinophil progenitors (EoPs) and basophil/mast cell progenitors (BMCPs) are prospectively isolatable in normal hematopoiesis, and that their lineage decisions are regulated principally by GATA-2 and C/EBPα. These progenitors were isolated downstream of granulocyte/monocyte progenitors (GMPs), and BMCPs further generated monopotent basophil progenitors (BaPs) and mast cell progenitors (MCPs). Gene expression analysis showed that neither GATA-1 nor GATA-2 was expressed in GMPs, whereas both of them were upregulated in EoPs, BMCPs, BaPs and MCPs. Importantly, C/EBPα was expressed in EoPs and BaPs as well as GMPs, but was downregulated in BMCPs and MCPs. We have reported that GATA-1 is critical primarily for megakaryocyte/erythrocyte commitment or conversion of stem and progenitor cells. We therefore focused on GATA-2 and C/EBPα functions in this study. Since both EoPs and BaPs co-expressed GATA-2 and C/EBPα while GMPs expressed only C/EBPα, we first transduced GATA-2 into GMPs via a GFP-tagged retrovirus. Strikingly, all GATA-2+ GMPs gave rise to pure eosinophil colonies but not basophil colonies, indicating that enforced GATA-2 can instruct GMPs to become EoPs. Next, since BMCPs only expressed GATA-2 but not C/EBPα, we maintained the expression of C/EBPα in GMPs by retroviral transduction. Interestingly, the sustained expression of C/EBPα blocked basophil/mast cell differentiation from GMPs, indicating that C/EBPα downregulation is required for GMPs to choose the basophil/mast cell fate. As a reciprocal experiment, we conditionally disrupted C/EBPα gene at the level of GMPs by retrovirally transducing Cre gene into GMPs purified from mice in which C/EBPα gene is flanked by loxP sequences (floxed: F). The frequency of mast cell read-out from C/EBPα-disrupted GMPs was 5-fold higher than that from C/EBPα F/F (Cre−) GMPs. C/EBPα-disrupted GMPs, however, did not give rise to BaPs. Furthermore, MCPs transduced with C/EBPα were converted into BaPs. Thus, C/EBPα is required to be reactivated during transition from BMCPs to BaPs. We further tested their interplay in specification of these lineages by using common lymphoid progenitors (CLPs), which do not express GATA-2 or C/EBPα. We enforced the expression of each transcription factor in CLPs in different orders by using the two-step retroviral transduction system. Interestingly, C/EBPα transduction reprogrammed CLPs into GM lineages, and subsequently-transduced GATA-2 instructed C/EBPα + CLPs to select the eosinophil fate. Next, we switched the order of transduction. Strikingly, GATA-2 transduction converted CLPs into BMCPs, and subsequently-transduced C/EBPα specified GATA-2+ CLPs to become BaPs. Thus, at the branchpoint for EoPs and BMCPs, GATA-2 upregulation instructed EoP development if C/EBPα was present, whereas it instructed BMCP development if C/EBPα was absent. After the BMCP stage, C/EBPα had to remain suppressed for MCP development, whereas BaPs developed by C/EBPα reactivation. These data collectively suggest that the order of expression of GATA-2 and C/EBPα is critical for their interplay to selectively activate developmental programs for the eosinophil, the basophil and the mast cell lineages.

scholarly journals Predictive Functions of H3K27me3 and H4K20me3 in Primate Hippocampal Stem and Progenitor Cells

2021 ◽  
Author(s):  
Christopher Rhodes ◽  
Chin Hsing Annie Lin
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Gene Activation ◽  
Protective Mechanism ◽  
Histone 3 ◽  
Stem And Progenitor Cells ◽  
Predictive Functions ◽  
Human Primate ◽  
Genomic Similarity

Epigenetic regulations play important roles in cell fate determination during neurogenesis, a process by which different types of neurons are generated from neural stem and progenitor cells (NSPCs). Although some epigenetic changes are part of developmental and aging processes, the role of tri-methylation on histone 3 lysine 27 (H3K27me3) and histone 4 lysine 20 (H4K20me3) in primate hippocampal NSPCs remains elusive. This task is best assessed within a context resembling the human brain. As more studies emerge, the baboon represents an excellent model of human central nervous system in addition to their genomic similarity. With a focus on H3K27me3 and H4K20me3, the overarching goal of this work is to reveal their respective epigenetic landscapes in NSPCs of non-human primate baboon hippocampus. We identified putative targets of H3K27me3 and H4K20me3 that suggests a protective mechanism by dual H3K27me3/H4K20me3-mediated repression of specific-lineage gene activation important for differentiation processes while controlling the progression of the cell cycle.

The role of cell lineage in development

1985 ◽  
Vol 312 (1153) ◽  
pp. 3-19 ◽  
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Evolutionary Divergence ◽  
Causative Role ◽  
Embryonic Cells ◽  
Developmental Potential ◽  
Cell Lineages

Studies of the role of cell lineage in development began in the latter part of the 19th century, fell into decline in the early part of the 20th, and were revived about 20 years ago. This recent revival was accompanied by the introduction of new and powerful analytical techniques. Concepts of importance for cell lineage studies include the principal division modes by which a cell may give rise to its descendant clone (proliferative, stem cell and diversifying); developmental determinacy , or indeterminacy , which refer to the degree to which the normal cleavage pattern of the early embryo and the developmental fate of its individual cells is, or is not, the same in specimen after specimen; commitment , which refers to the restriction of the developmental potential of a pluripotent embryonic cell; and equivalence group , which refers to two or more equivalently pluripotent cell clones that normally take on different fates but of which under abnormal conditions one clone can take on the fate of another. Cell lineage can be inferred to have a causative role in developmental cell fate in embryos in which induced changes in cell division patterns lead to changes in cell fate. Moreover, such a causative role of cell lineage is suggested by cases where homologous cell types characteristic of a symmetrical and longitudinally metameric body plan arise via homologous cell lineages. The developmental pathways of commitment to particular cell fates proceed according to a mixed typologic and topographic hierarchy, which appears to reflect an evolutionary compromise between maximizing the ease of ordering the spatial distribution of the determinants of commitment and minimizing the need for migration of differentially committed embryonic cells. Comparison of the developmental cell lineages in leeches and insects indicates that the early course of embryogenesis is radically different in these phyletically related taxa. This evolutionary divergence of the course of early embryogenesis appears to be attributable to an increasing prevalence of polyclonal rather than monoclonal commitment in the phylogenetic line leading from an annelid-like ancestor to insects.

scholarly journals Heterochromatin and Polycomb as regulators of haematopoiesis

2021 ◽  
Vol 49 (2) ◽  
pp. 805-814
Author(s):  
Christine R. Keenan
Keyword(s):  
Cell Cycle ◽  
Epigenetic Silencing ◽  
Haematological Malignancies ◽  
Facultative Heterochromatin ◽  
Therapeutic Targeting ◽  
Self Renewal ◽  
Haematopoietic Stem Cells ◽  
Cell Cycle Genes ◽  
Age Related

Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin: H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). This review will discuss the role of these distinct epigenetic silencing mechanisms in regulating normal haematopoiesis, how these contribute to age-related haematopoietic dysfunction, and the rationale for therapeutic targeting of these pathways in the treatment of haematological malignancies.

scholarly journals PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ashok Arasu ◽  
Sengottuvelan Murugan ◽  
Musthafa Mohamed Essa ◽  
Thirunavukkarasu Velusamy ◽  
Gilles J. Guillemin
Keyword(s):  
Tumor Suppressor ◽  
Cell Fate ◽  
Cancer Progression ◽  
Tumor Suppressor Function ◽  
Aberrant Expression ◽  
Tissue Specific ◽  
Cell Lineages ◽  
Neurodevelopmental Disease ◽  
Potential Link

Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

scholarly journals Unique roles of ATAC and SAGA - KAT2A complexes in normal and malignant hematopoiesis

2020 ◽  
Author(s):  
Liliana Arede ◽  
Elena Foerner ◽  
Selinde Wind ◽  
Rashmi Kulkarni ◽  
Ana Filipa Domingues ◽  
...  
Keyword(s):  
Cell Fate ◽  
Histone Acetyltransferase ◽  
Leukemia Stem Cell ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Epigenetic Regulator ◽  
Significant Research ◽  
Histone Modifiers ◽  
Stem And Progenitor Cells

ABSTRACTEpigenetic histone modifiers are key players in cell fate decisions. Significant research has focused on their enzymatic activity, but less is known about the contextual role of the complexes they integrate. We focus on KAT2A, a histone acetyltransferase we recently associated with leukemia stem cell maintenance, and which participates in ATAC and SAGA complexes. We show that ATAC is uniquely required for maintenance of normal and leukemia stem and progenitor cells, while SAGA more specifically contributes to cell identity. This dichotomy sets a paradigm for investigating epigenetic activities in their macromolecular context and informs epigenetic regulator targeting for translational purposes.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

“Quasi industre giardiniero”

2016 ◽  
Vol 33 (4) ◽  
pp. 522-568
Author(s):  
Cory M. Gavito
Keyword(s):  
Complex Nature ◽  
Editorial Process ◽  
Fluid Exchange ◽  
Oral Transmission ◽  
Musical Practices

Among the roughly 150 Italian songbooks published between 1610 and 1665 with the guitar tablature known as alfabeto, about thirteen are anthologies. These anthologies often advertise the role of a compiler who has gathered together music by diverse authors. The extent to which compilers also functioned as authors and editors is not well understood. This essay considers the case of Giovanni Stefani, a compiler who, in the preface to his Scherzi amorosi of 1622, describes the anthology as a collection of his choosing that contains “varie compositioni de Virtuosi della prima classe” (various compositions of first-class virtuosos). Intriguingly, none of the settings Stefani prints (in both this alfabeto anthology and two others) include attributions. Since the 1880s, scholars have been preoccupied with matters of transmission and attribution, unearthing a network of textual and musical concordances. This article expands the nexus of Stefani’s songs and their concordant sources, revealing an array of examples that range from identical copies to “partial” concordances that take over motives, phrases, refrains, or harmonic schemes. These examples indicate that in preparing his anthologies, Stefani mined a corpus of existing prints and manuscripts while also relying heavily on oral transmission. The complex nature of Stefani’s approach, taken together with his complete avoidance of composer attributions, points toward an editorial process shaped by a fluid exchange between oral and written musical practices.

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