scholarly journals Breaking symmetry: the asymmetries in epigenetic inheritance

2021 ◽  
Vol 43 (1) ◽  
pp. 14-19
Author(s):  
Emily Zion ◽  
Xin Chen
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Genetic Information ◽  
Asymmetric Cell Division ◽  
Epigenetic Inheritance ◽  
Multicellular Organism ◽  
Epigenetic Information ◽  
Distinct Cell ◽  
Stem Cell Division

Symmetry and asymmetry are the fundamental aspects of life. Most cells within a multicellular organism contain the same genetic information, passed on from one originating cell, the zygote; however, these cells can take on a variety of different identities, with diverse appearances and functions. A fundamental question in biology ponders how cells containing identical DNA content can take on different cell identities. Epigenetic mechanisms could be the symmetry-breaking factor, as they are able to change the gene expression in cells without changing the DNA sequence. While the process of duplication and segregation of DNA during cell division has been well studied, it is less understood how the epigenetic information is established and inherited in the cells within a multicellular organism. Studies of asymmetric stem cell division, where a stem cell division gives rise to a self-renewed stem cell and a differentiating daughter cell, provide a model to study how epigenetic information is maintained or changed to produce daughter cells with identical genetic information but distinct cell fates. Here, we discuss the findings and ideas of how epigenetic information is maintained or changed during asymmetric cell division and the importance of this asymmetry in influencing cell fate.

scholarly journals Ankle2, A Target of Zika Virus, Controls Asymmetric Cell Division of Neuroblasts and Uncovers a Novel Microcephaly Pathway

2019 ◽  
Author(s):  
N. Link ◽  
H. Chung ◽  
A. Jolly ◽  
M. Withers ◽  
B. Tepe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Nuclear Envelope ◽  
Cell Fate ◽  
Zika Virus ◽  
Asymmetric Cell Division ◽  
Brain Size ◽  
Stem Cell Division ◽  
Fate Determinants ◽  
Cell Fate Determinants

ABSTRACTNeuroblasts in flies divide asymmetrically by establishing polarity, distributing cell fate determinants asymmetrically, and positioning their spindle for cell division. The apical complex contains aPKC, Bazooka (Par3), and Par6, and its activity depends on L(2)gl. We show that Ankle2 interacts with L(2)gl and affects aPKC. Reducing Ankle2 levels disrupts ER and nuclear envelope morphology, releasing the kinase Ballchen/VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par complex localization, and spindle alignment defects. Importantly, removal of one copy ofballchen/VRK1orl(2)glsuppresses the loss ofAnkle2and restores viability and brain size. The Zika virus NS4A protein interacts withDrosophilaAnkle2 and VRK1 in dividing neuroblasts. Human mutational studies implicate this neural cell division pathway in microcephaly and motor neuron disease. In summary, NS4A, ANKLE2, VRK1 and LLGL1 define a novel pathway that impinges on asymmetric determinants of neural stem cell division.

scholarly journals Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in Drosophila male germline stem cell division

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Cuie Chen ◽  
Mayu Inaba ◽  
Zsolt G Venkei ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Mother And Daughter ◽  
Stem Cell Divisions ◽  
Stem Cell Division ◽  
Male Germline Stem Cells

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

Strontium regulates stem cell fate during osteogenic differentiation through asymmetric cell division

2021 ◽  
Vol 119 ◽  
pp. 432-443
Author(s):  
Yanqun Li ◽  
Jianhui Yue ◽  
Yuan Liu ◽  
Jun Wu ◽  
Min Guan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Stem Cell Fate

scholarly journals Emerging mechanisms of asymmetric stem cell division

2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Binary Outcomes ◽  
Cellular Mechanisms ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Dividing Cells ◽  
Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

scholarly journals Cytoskeletal Control and Wnt Signaling—APC’s Dual Contributions in Stem Cell Division and Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3811
Author(s):  
M. Angeles Juanes
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Extracellular Signals ◽  
Integrative View ◽  
Molecular Determinants ◽  
Stem Cell Division ◽  
Outstanding Question ◽  
Stem Cell Pool

Intestinal epithelium architecture is sustained by stem cell division. In principle, stem cells can divide symmetrically to generate two identical copies of themselves or asymmetrically to sustain tissue renewal in a balanced manner. The choice between the two helps preserve stem cell and progeny pools and is crucial for tissue homeostasis. Control of spindle orientation is a prime contributor to the specification of symmetric versus asymmetric cell division. Competition for space within the niche may be another factor limiting the stem cell pool. An integrative view of the multiple links between intracellular and extracellular signals and molecular determinants at play remains a challenge. One outstanding question is the precise molecular roles of the tumour suppressor Adenomatous polyposis coli (APC) for sustaining gut homeostasis through its respective functions as a cytoskeletal hub and a down regulator in Wnt signalling. Here, we review our current understanding of APC inherent activities and partners in order to explore novel avenues by which APC may act as a gatekeeper in colorectal cancer and as a therapeutic target.

scholarly journals Wnt-and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sergi Junyent ◽  
Joshua C Reeves ◽  
James LA Szczerkowski1 ◽  
Clare L Garcin ◽  
Tung-Jui Trieu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Glutamate Receptors ◽  
Cell Fate ◽  
Cell Biology ◽  
Wnt Pathway ◽  
Asymmetric Cell Division ◽  
Cell Signalling ◽  
Embryonic Stem ◽  
Kainate Receptors

The Wnt-pathway is part of a signalling network that regulates many aspects of cell biology. Recently we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs). Here, we demonstrate that this crosstalk persists throughout the Wnt3a-response in ESCs. Both AMPA- and Kainate-receptors regulate early Wnt3a-recruitment, dynamics on the cell membrane, and orientation of the spindle towards a Wnt3a-source at mitosis. AMPA-receptors specifically are required for segregating cell fate components during Wnt3a-mediated asymmetric cell division (ACD). Using Wnt-pathway component knockout lines, we determine that Wnt co-receptor Lrp6 has particular functionality over Lrp5 in cytoneme formation, and in facilitating ACD. Both Lrp5 and 6, alongside pathway effector β-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localized Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

The Significant Role of Centrosomes in Stem Cell Division and Differentiation

2011 ◽  
Vol 17 (4) ◽  
pp. 506-512 ◽  
Author(s):  
Heide Schatten ◽  
Qing-Yuan Sun
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Primary Cilia ◽  
Asymmetric Cell Division ◽  
Embryonic Stem ◽  
Stem Cell Maintenance ◽  
Tissue Repair And Regeneration ◽  
Mother And Daughter ◽  
Stem Cell Division

AbstractThe role of centrosomes in stem cell division has recently been highlighted and further ascribes important functions to centrosomes in stem cell maintenance, cellular differentiation, and development. Advanced cell and molecular studies coupled with immunofluorescence, electron microscopy, and live cell imaging of specific centrosome proteins have contributed greatly to our knowledge of centrosome composition, structure, and dynamics and have uncovered new insights into mechanisms of centrosome functions in asymmetric cell division. The establishment of asymmetry and differential positioning of mother and daughter centrosomes during stem cell mitosis is important for allowing one cell to maintain stem cell characteristics while the sibling cell undergoes differentiation. Another key role for centrosomes has been revealed in primary cilia of embryonic stem cells that play significant roles in cellular signaling and are therefore critically important for stem cell decisions. Studies of signaling through primary cilia may contribute important information that may aid in the production of specific cells that are suitable for tissue repair and regeneration in the field of regenerative medicine.

scholarly journals Asymmetric assembly of centromeres epigenetically regulates stem cell fate

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Anna Ada Dattoli ◽  
Ben L. Carty ◽  
Antje M. Kochendoerfer ◽  
Conall Morgan ◽  
Annie E. Walshe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Germline Stem Cells ◽  
Differentiated Cells ◽  
Oocyte Meiosis ◽  
Assembly Factor ◽  
Stem Cell Division ◽  
Female Germline ◽  
Centromere Assembly

Centromeres are epigenetically defined by CENP-A–containing chromatin and are essential for cell division. Previous studies suggest asymmetric inheritance of centromeric proteins upon stem cell division; however, the mechanism and implications of selective chromosome segregation remain unexplored. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres after replication and before segregation. Specifically, CENP-A deposition is promoted by CYCLIN A, while excessive CENP-A deposition is prevented by CYCLIN B, through the HASPIN kinase. Furthermore, chromosomes inherited by GSCs incorporate more CENP-A, making stronger kinetochores that capture more spindle microtubules and bias segregation. Importantly, symmetric incorporation of CENP-A on sister chromatids via HASPIN knockdown or overexpression of CENP-A, either alone or together with its assembly factor CAL1, drives stem cell self-renewal. Finally, continued CENP-A assembly in differentiated cells is nonessential for egg development. Our work shows that centromere assembly epigenetically drives GSC maintenance and occurs before oocyte meiosis.

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