scholarly journals Centrosome age regulates kinetochore–microtubule stability and biases chromosome mis-segregation

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ivana Gasic ◽  
Purnima Nerurkar ◽  
Patrick Meraldi
Keyword(s):  
Stem Cell ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Human Cells ◽  
Functional Asymmetry ◽  
Mitotic Spindles ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Microtubule Stability ◽  
Stem Cell Divisions

The poles of the mitotic spindle contain one old and one young centrosome. In asymmetric stem cell divisions, the age of centrosomes affects their behaviour and their probability to remain in the stem cell. In contrast, in symmetric divisions, old and young centrosomes are thought to behave equally. This hypothesis is, however, untested. In this study, we show in symmetrically dividing human cells that kinetochore–microtubules associated to old centrosomes are more stable than those associated to young centrosomes, and that this difference favours the accumulation of premature end-on attachments that delay the alignment of polar chromosomes at old centrosomes. This differential microtubule stability depends on cenexin, a protein enriched on old centrosomes. It persists throughout mitosis, biasing chromosome segregation in anaphase by causing daughter cells with old centrosomes to retain non-disjoint chromosomes 85% of the time. We conclude that centrosome age imposes via cenexin a functional asymmetry on all mitotic spindles.

scholarly journals Epithelial polarity and spindle orientation: intersecting pathways

2013 ◽  
Vol 368 (1629) ◽  
pp. 20130291 ◽  
Author(s):  
Dan T. Bergstralh ◽  
Timm Haack ◽  
Daniel St Johnston
Keyword(s):  
Epithelial Cells ◽  
Cell Fate ◽  
Spindle Orientation ◽  
Mitotic Spindles ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Discs Large ◽  
Stem Cell Divisions ◽  
Fate Determinants ◽  
Cell Fate Determinants

During asymmetric stem cell divisions, the mitotic spindle must be correctly oriented and positioned with respect to the axis of cell polarity to ensure that cell fate determinants are appropriately segregated into only one daughter cell. By contrast, epithelial cells divide symmetrically and orient their mitotic spindles perpendicular to the main apical–basal polarity axis, so that both daughter cells remain within the epithelium. Work in the past 20 years has defined a core ternary complex consisting of Pins, Mud and Gαi that participates in spindle orientation in both asymmetric and symmetric divisions. As additional factors that interact with this complex continue to be identified, a theme has emerged: there is substantial overlap between the mechanisms that orient the spindle and those that establish and maintain apical–basal polarity in epithelial cells. In this review, we examine several factors implicated in both processes, namely Canoe, Bazooka, aPKC and Discs large, and consider the implications of this work on how the spindle is oriented during epithelial cell divisions.

scholarly journals A hybrid model connecting regulatory interactions with stem cell divisions in the root

2021 ◽  
Vol 2 ◽  
Author(s):  
Lisa Van den Broeck ◽  
Ryan J. Spurney ◽  
Adam P. Fisher ◽  
Michael Schwartz ◽  
Natalie M. Clark ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hybrid Model ◽  
Regulatory Networks ◽  
Quiescent Center ◽  
Specific Expression ◽  
Agent Based ◽  
Cell Divisions ◽  
Cell Type Specific Expression ◽  
Stem Cell Divisions ◽  
Cell Niche

Abstract Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2875-2888 ◽  
Author(s):  
L.A. Wrischnik ◽  
C.J. Kenyon
Keyword(s):  
Stem Cell ◽  
Regulatory Gene ◽  
Epidermal Cells ◽  
Body Axis ◽  
Wild Type ◽  
Hox Gene ◽  
C Elegans ◽  
Cell Divisions ◽  
Body Regions ◽  
Stem Cell Divisions

In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.

scholarly journals Symmetric vs. Asymmetric Stem Cell Divisions: An Adaptation against Cancer?

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76195 ◽  
Author(s):  
Leili Shahriyari ◽  
Natalia L. Komarova
Keyword(s):  
Stem Cell ◽  
Cell Divisions ◽  
Stem Cell Divisions

scholarly journals The equatorial position of the metaphase plate ensures symmetric cell divisions

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Chia Huei Tan ◽  
Ivana Gasic ◽  
Sabina P Huber-Reggi ◽  
Damian Dudka ◽  
Marin Barisic ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Metaphase Plate ◽  
Spindle Assembly ◽  
Equatorial Position ◽  
Asymmetric Cell Divisions ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Microtubule Stability ◽  
Chromosome Alignment ◽  
Metazoan Cell

Chromosome alignment in the middle of the bipolar spindle is a hallmark of metazoan cell divisions. When we offset the metaphase plate position by creating an asymmetric centriole distribution on each pole, we find that metaphase plates relocate to the middle of the spindle before anaphase. The spindle assembly checkpoint enables this centering mechanism by providing cells enough time to correct metaphase plate position. The checkpoint responds to unstable kinetochore–microtubule attachments resulting from an imbalance in microtubule stability between the two half-spindles in cells with an asymmetric centriole distribution. Inactivation of the checkpoint prior to metaphase plate centering leads to asymmetric cell divisions and daughter cells of unequal size; in contrast, if the checkpoint is inactivated after the metaphase plate has centered its position, symmetric cell divisions ensue. This indicates that the equatorial position of the metaphase plate is essential for symmetric cell divisions.

scholarly journals Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal

Cell Systems ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 640-652.e5 ◽  
Author(s):  
Fumio Arai ◽  
Patrick S. Stumpf ◽  
Yoshiko M. Ikushima ◽  
Kentaro Hosokawa ◽  
Aline Roch ◽  
...  
Keyword(s):  
Machine Learning ◽  
Stem Cell ◽  
Daughter Cell ◽  
Expression Profiles ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Divisions ◽  
Stem Cell Divisions ◽  
Effects Of Aging ◽  
Cell Expression

scholarly journals Monoassociation withLactobacillus plantarumDisrupts Intestinal Homeostasis in AdultDrosophila melanogaster

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
David Fast ◽  
Aashna Duggal ◽  
Edan Foley
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Simple Model ◽  
Life Span ◽  
Lactobacillus Plantarum ◽  
Adult Longevity ◽  
Intestinal Homeostasis ◽  
Content Type ◽  
Cell Divisions ◽  
Stem Cell Divisions

ABSTRACTAdultDrosophila melanogasterraised in the absence of symbiotic bacteria have fewer intestinal stem cell divisions and a longer life span than their conventionally reared counterparts. However, we do not know if increased stem cell divisions are essential for symbiont-dependent regulation of longevity. To determine if individual symbionts cause aging-dependent death inDrosophila, we examined the impacts of common symbionts on host longevity. We found that monoassociation of adultDrosophilawithLactobacillus plantarum, a widely reported fly symbiont and member of the probioticLactobacillusgenus, curtails adult longevity relative to germfree counterparts. The effects ofLactobacillus plantarumon life span were independent of intestinal aging. Instead, we found that association withLactobacillus plantarumcauses an extensive intestinal pathology within the host, characterized by loss of stem cells, impaired epithelial renewal, and a gradual erosion of epithelial ultrastructure. Our study uncovers an unknown aspect ofLactobacillus plantarum-Drosophilainteractions and establishes a simple model to characterize symbiont-dependent disruption of intestinal homeostasis.IMPORTANCEUnder homeostatic conditions, gut bacteria provide molecular signals that support the organization and function of the host intestine. Sudden shifts in the composition or distribution of gut bacterial communities impact host receipt of bacterial cues and disrupt tightly regulated homeostatic networks. We used theDrosophila melanogastermodel to determine the effects of prominent fly symbionts on host longevity and intestinal homeostasis. We found that monoassociation withLactobacillus plantarumleads to a loss of intestinal progenitor cells, impaired epithelial renewal, and disruption of gut architecture as flies age. These observations uncover a novel phenotype caused by monoassociation of a germfree host with a common symbiont and establish a simple model to characterize symbiont-dependent loss of intestinal homeostasis.

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