Faculty Opinions recommendation of Asymmetric Centromeres Differentially Coordinate with Mitotic Machinery to Ensure Biased Sister Chromatid Segregation in Germline Stem Cells.

Although non-random sister chromatid segregation has been proposed to underlie asymmetric cell divisions, the underlying biological significance or mechanisms remained elusive. Here we show that non-random sister chromatid segregation during asymmetric division of Drosophila male germline stem cells is mediated by ribosomal DNA (rDNA) loci, consisting of hundreds of tandemly repeated rDNA units. We identify a novel zinc-finger protein CG2199/Indra that binds to rDNA and control non-random sister chromatid segregation. Our data indicate that non-random sister chromatid segregation may reflect the segregation of sister chromatids with different rDNA copy numbers after unequal sister chromatid exchange to maintain rDNA copy number through generations. To our knowledge, this is the first study to provide mechanistic insights into the mechanism of non-random sister chromatid segregation.

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Ribosomal DNA and the rDNA-binding protein Indra mediate non-random sister chromatid segregation in Drosophila male germline stem cells

10.1242/prelights.6514 ◽

2018 ◽

Author(s):

Maiko Kitaoka

Keyword(s):

Stem Cells ◽

Ribosomal Dna ◽

Sister Chromatid ◽

Binding Protein ◽

Germline Stem Cells ◽

Male Germline ◽

Chromatid Segregation ◽

Male Germline Stem Cells

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Asymmetric Centromeres Differentially Coordinate with Mitotic Machinery to Ensure Biased Sister Chromatid Segregation in Germline Stem Cells

Cell Stem Cell ◽

10.1016/j.stem.2019.08.014 ◽

2019 ◽

Vol 25 (5) ◽

pp. 666-681.e5 ◽

Cited By ~ 12

Author(s):

Rajesh Ranjan ◽

Jonathan Snedeker ◽

Xin Chen

Keyword(s):

Stem Cells ◽

Sister Chromatid ◽

Germline Stem Cells ◽

Chromatid Segregation

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

Essays in Biochemistry ◽

10.1042/ebc20190066 ◽

2020 ◽

Vol 64 (2) ◽

pp. 223-232 ◽

Cited By ~ 1

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.

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Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells

Symmetry ◽

10.3390/sym12111868 ◽

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.

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