scholarly journals Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells

Symmetry ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1868
Author(s):  
Krishnanchali Panchalingam ◽  
Laura Jacox ◽  
Benjamin D. Cappiello ◽  
James L. Sherley
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Sister Chromatid ◽  
Human Tissue ◽  
Cell Kinetics ◽  
Genetic Fidelity ◽  
Cell Strain ◽  
Hepatic Stem Cell ◽  
Sister Chromatids ◽  
Chromatid Segregation

The loss of genetic fidelity in tissue stem cells is considered a significant cause of human aging and carcinogenesis. Many cellular mechanisms are well accepted for limiting mutations caused by replication errors and DNA damage. However, one mechanism, non-random sister chromatid segregation, remains controversial. This atypical pattern of chromosome segregation is restricted to asymmetrically self-renewing cells. Though first confirmed in murine cells, non-random segregation was originally proposed by Cairns as an important genetic fidelity mechanism in human tissues. We investigated human hepatic stem cells expanded by suppression of asymmetric cell kinetics (SACK) for evidence of non-random sister chromatid segregation. Cell kinetics and time-lapse microscopy analyses established that an ex vivo expanded human hepatic stem cell strain possessed SACK agent-suppressible asymmetric cell kinetics. Complementary DNA strand-labeling experiments revealed that cells in hepatic stem cell cultures segregated sister chromatids non-randomly. The number of cells cosegregating sister chromatids with the oldest “immortal DNA strands” was greater under conditions that increased asymmetric self-renewal kinetics. Detection of this mechanism in a human tissue stem cell strain increases support for Cairns’ proposal that non-random sister chromatid segregation operates in human tissue stem cells to limit carcinogenesis.

scholarly journals Stem cell mitotic drive ensures asymmetric epigenetic inheritance

2018 ◽  
Author(s):  
Rajesh Ranjan ◽  
Jonathan Snedeker ◽  
Xin Chen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Sister Chromatid ◽  
Germline Stem Cell ◽  
Cell Fates ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Distinct Cell

SUMMARYThrough the process of symmetric cell division, one mother cell gives rise to two identical daughter cells. Many stem cells utilize asymmetric cell division (ACD) to produce a self-renewed stem cell and a differentiating daughter cell. Since both daughter cells inherit the identical genetic information during ACD, a crucial question concerns how non-genic factors could be inherited differentially to establish distinct cell fates. It has been hypothesized that epigenetic differences at sister centromeres could contribute to biased sister chromatid attachment and segregation. However, direct in vivo evidence has never been shown. Here, we report that a stem cell-specific ‘mitotic drive’ ensures biased sister chromatid attachment and segregation. We have found during stem cell ACD, sister centromeres become asymmetrically enriched with proteins involved in centromere specification and kinetochore function. Furthermore, we show that that temporally asymmetric microtubule activities direct polarized nuclear envelope breakdown, allowing for the preferential recognition and attachment of microtubules to asymmetric sister kinetochores and sister centromeres. This communication occurs in a spatiotemporally regulated manner. Abolishment of either the establishment of asymmetric sister centromeres or the asymmetric microtubule emanation results in randomized sister chromatid segregation, which leads to stem cell loss. Our results demonstrate that the cis-asymmetry at sister centromeres tightly coordinates with the trans-asymmetry from the mitotic machinery to allow for differential attachment and segregation of genetically identical yet epigenetically distinct sister chromatids. Together, these results provide the first direct in vivo mechanisms for partitioning epigenetically distinct sister chromatids in asymmetrically dividing stem cells, which opens a new direction to study how this mechanism could be used in other developmental contexts to achieve distinct cell fates through mitosis.One Sentence SummaryDuring Drosophila male germline stem cell asymmetric division, sister centromeres communicate with spindle microtubules for differential attachment and segregation of sister chromatids.

Centromere assembly and non-random sister chromatid segregation in stem cells

2020 ◽  
Vol 64 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Ben L. Carty ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Sister Chromatid ◽  
Asymmetric Cell Division ◽  
Protein A ◽  
Germline Stem Cells ◽  
Sister Chromatids ◽  
Centromere Protein A ◽  
Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

scholarly journals Responsiveness of Hematopoietic Tissue to Erythropoietin in Relation to the Time of Administration and Duration of Action of the Hormone

Blood ◽  
1965 ◽  
Vol 25 (5) ◽  
pp. 795-808 ◽  
Author(s):  
JOHN C. SCHOOLEY
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Life Cycle ◽  
Cell Kinetics ◽  
Limited Time ◽  
Hematopoietic Tissue ◽  
Duration Of Action ◽  
Time Of Administration ◽  
Different Doses

Abstract Following the injection of erythropoietin either in a single large dose or in multiple doses, a change in the responsiveness of the hematopoietic tissue occurs. The fact that different doses of erythropoietin stimulate erythropoiesis to the same extent when the action of the hormone is limited to 6 hours by the injection of antibody suggests that the stem cells are receptive to the action of erythropoietin only at some limited time in their individual life cycle. It is suggested that this period is sometime after metaphase and before the commencement of DNA synthesis in the interphase state of individual stem cells. It is further suggested that the increased responsiveness of the hematopoietic tissue to erythropoietin following injection is due to recruitment of stem cells into this receptive state. This recruitment may be due to both the division of stem cells and the movement of cells through cell cycle into the receptive state. The results are discussed in relation to two recent models of stem cell kinetics.

scholarly journals CENP-C regulates centromere assembly, asymmetry and epigenetic age in Drosophila germline stem cells

2020 ◽  
Author(s):  
Ben L Carty ◽  
Anna A Dattoli ◽  
Elaine M Dunleavy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Germ Line ◽  
Asymmetric Distribution ◽  
Germline Stem Cells ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Asymmetric Divisions ◽  
Centromere Assembly

AbstractGermline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila germ line stem cells (GSCs), it has recently been shown that the centromeric histone CENP-A (called CID in flies) - the epigenetic determinant of centromere identity - is asymmetrically distributed between sister chromatids. In these cells, CID deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. Here we report that the inner kinetochore protein CENP-C, is required for the assembly of CID in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CID between stem and daughter cells. In addition, we find that CID is lost from centromeres in aged GSCs and that a reduction in CENP-C accelerates this loss. Finally, we show that CENP-C depletion in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required to sustain asymmetric divisions in female Drosophila GSCs.

scholarly journals CENP-C functions in centromere assembly, the maintenance of CENP-A asymmetry and epigenetic age in Drosophila germline stem cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (5) ◽  
pp. e1009247
Author(s):  
Ben L. Carty ◽  
Anna A. Dattoli ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Germ Line ◽  
Asymmetric Distribution ◽  
Germline Stem Cells ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Asymmetric Divisions ◽  
Centromere Assembly

Germline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila germ line stem cells (GSCs), it has recently been shown that the centromeric histone CENP-A (called CID in flies)—the epigenetic determinant of centromere identity—is asymmetrically distributed between sister chromatids. In these cells, CID deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. Here we report that the inner kinetochore protein CENP-C, is required for the assembly of CID in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CID between stem and daughter cells. In addition, we find that CID is lost from centromeres in aged GSCs and that a reduction in CENP-C accelerates this loss. Finally, we show that CENP-C depletion in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required to sustain asymmetric divisions in female Drosophila GSCs.

Clonal expansion of adult rat hepatic stem cell lines by suppression of asymmetric cell kinetics (SACK)

2003 ◽  
Vol 83 (7) ◽  
pp. 760-771 ◽  
Author(s):  
Hsuan-Shu Lee ◽  
Gracy G. Crane ◽  
Joshua R. Merok ◽  
James R. Tunstead ◽  
Nicole L. Hatch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Cell Kinetics ◽  
Clonal Expansion ◽  
Adult Rat ◽  
Hepatic Stem Cell ◽  
Stem Cell Lines

scholarly journals Stem cells: the new “model organism”

2017 ◽  
Vol 28 (11) ◽  
pp. 1409-1411 ◽  
Author(s):  
David G. Drubin ◽  
Anthony A. Hyman
Keyword(s):  
Stem Cells ◽  
Tissue Culture ◽  
Stem Cell ◽  
Human Tissue ◽  
Cell Biology ◽  
Physiological Function ◽  
Model Organism ◽  
Culture Cells ◽  
Tissue Culture Cells ◽  
Biology Research

Human tissue culture cells have long been a staple of molecular and cell biology research. However, although these cells are derived from humans, they have often lost considerable aspects of natural physiological function. Here we argue that combined advances in genome editing, stem cell production, and organoid derivation from stem cells represent a revolution in cell biology. These advances have important ramifications for the study of basic cell biology mechanisms, as well as for the ways in which discoveries in mechanisms are translated into understanding of disease.

scholarly journals Asymmetric Cell Kinetics Genes: The Key to Expansion of Adult Stem Cells in Culture

2002 ◽  
Vol 2 ◽  
pp. 1906-1921 ◽  
Author(s):  
James L. Sherley
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Kinetics ◽  
Embryonic Stem ◽  
Adult Stem Cell ◽  
Cellular Mechanisms ◽  
Cells In Culture ◽  
Somatic Tissues ◽  
Kinetics Of

A singular challenge in stem cell research today is the expansion and propagation of functional adult stem cells. Unlike embryonic stem cells, which are immortal in culture, adult stem cells are notorious for the difficulty encountered when attempts are made to expand them in culture. One overlooked reason for this difficulty may be the inherent asymmetric cell kinetics of stem cells in postnatal somatic tissues. Senescence is the expected fate of a culture whose growth depends on adult stem cells that divide with asymmetric cell kinetics. Therefore, the bioengineering of strategies to expand adult stem cells in culture requires knowledge of cellular mechanisms that control asymmetric cell kinetics. The properties of several genes recently implicated to function in a cellular pathway(s) that regulates asymmetric cell kinetics are discussed. Understanding the function of these genes in asymmetric cell kinetics mechanisms may be the key that unlocks the adult stem cell expansion problem.

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