scholarly journals Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

2017 ◽  
Author(s):  
Cuie Chen ◽  
Ryan Cummings ◽  
Aghapi Mordovanakis ◽  
Alan J. Hunt ◽  
Michael Mayer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Adult Stem Cells ◽  
Asymmetric Cell Division ◽  
Cytokine Receptor ◽  
Spindle Orientation ◽  
Germline Stem Cells ◽  
Self Renewal

AbstractAsymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.

scholarly journals Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Cuie Chen ◽  
Ryan Cummings ◽  
Aghapi Mordovanakis ◽  
Alan J Hunt ◽  
Michael Mayer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Adult Stem Cells ◽  
Asymmetric Cell Division ◽  
Cytokine Receptor ◽  
Spindle Orientation ◽  
Germline Stem Cells ◽  
Self Renewal

Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.

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 The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mayu Inaba ◽  
Zsolt G Venkei ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Polarity ◽  
Asymmetric Cell Division ◽  
Underlying Mechanism ◽  
Germline Stem Cells ◽  
Cell Fates ◽  
Male Germline ◽  
Distinct Cell ◽  
Tightly Coupled

Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD.

scholarly journals Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Antje M. Kochendoerfer ◽  
Federica Modafferi ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Chromosome Segregation ◽  
Asymmetric Cell Division ◽  
Genetic Material ◽  
Asymmetric Distribution ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Male Germline Stem Cells

The centromere is the constricted chromosomal region required for the correct separation of the genetic material at cell division. The kinetochore protein complex assembles at the centromere and captures microtubules emanating from the centrosome to orchestrate chromosome segregation in mitosis and meiosis. Asymmetric cell division (ACD) is a special type of mitosis that generates two daughter cells with different fates. Epigenetic mechanisms operating at the centromere have been proposed to contribute to ACD. Recent studies have shown that an asymmetric distribution of CENP-A—the centromere-specific histone H3 variant—between sister chromatids can bias chromosome segregation in ACD. In stem cells, this leads to non-random sister chromatid segregation, which can affect cell fate. These findings support the ‘silent sister' hypothesis, according to which the mechanisms of ACD are epigenetically regulated through centromeres. Here, we review the recent data implicating centromeres in ACDs and cell fate in Drosophila melanogaster female and male germline stem cells.

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.

scholarly journals Drosophila neuroblasts as a new model for the study of stem cell self-renewal and tumour formation

2014 ◽  
Vol 34 (4) ◽  
Author(s):  
Song Li ◽  
Hongyan Wang ◽  
Casper Groth
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Cell Fate Specification ◽  
Larval Brain ◽  
Self Renewal ◽  
Intrinsic Factors ◽  
Tumour Formation

Drosophila larval brain stem cells (neuroblasts) have emerged as an important model for the study of stem cell asymmetric division and the mechanisms underlying the transformation of neural stem cells into tumour-forming cancer stem cells. Each Drosophila neuroblast divides asymmetrically to produce a larger daughter cell that retains neuroblast identity, and a smaller daughter cell that is committed to undergo differentiation. Neuroblast self-renewal and differentiation are tightly controlled by a set of intrinsic factors that regulate ACD (asymmetric cell division). Any disruption of these two processes may deleteriously affect the delicate balance between neuroblast self-renewal and progenitor cell fate specification and differentiation, causing neuroblast overgrowth and ultimately lead to tumour formation in the fly. In this review, we discuss the mechanisms underlying Drosophila neural stem cell self-renewal and differentiation. Furthermore, we highlight emerging evidence in support of the notion that defects in ACD in mammalian systems, which may play significant roles in the series of pathogenic events leading to the development of brain cancers.

scholarly journals PLK-1 Regulation of Asymmetric Cell Division in the Early C. elegans Embryo

2021 ◽  
Vol 8 ◽  
Author(s):  
Amelia J. Kim ◽  
Erik E. Griffin
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Critical Role ◽  
Cell Cortex ◽  
C Elegans ◽  
Mitotic Kinase ◽  
Centrosome Separation

PLK1 is a conserved mitotic kinase that is essential for the entry into and progression through mitosis. In addition to its canonical mitotic functions, recent studies have characterized a critical role for PLK-1 in regulating the polarization and asymmetric division of the one-cell C. elegans embryo. Prior to cell division, PLK-1 regulates both the polarization of the PAR proteins at the cell cortex and the segregation of cell fate determinants in the cytoplasm. Following cell division, PLK-1 is preferentially inherited to one daughter cell where it acts to regulate the timing of centrosome separation and cell division. PLK1 also regulates cell polarity in asymmetrically dividing Drosophila neuroblasts and during mammalian planar cell polarity, suggesting it may act broadly to connect cell polarity and cell cycle mechanisms.

scholarly journals Author response: Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

2018 ◽  
Author(s):  
Cuie Chen ◽  
Ryan Cummings ◽  
Aghapi Mordovanakis ◽  
Alan J Hunt ◽  
Michael Mayer ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Polarity ◽  
Asymmetric Cell Division ◽  
Cytokine Receptor ◽  
Author Response

scholarly journals Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells

2013 ◽  
Vol 201 (3) ◽  
pp. 409-425 ◽  
Author(s):  
An Zeng ◽  
Yong-Qin Li ◽  
Chen Wang ◽  
Xiao-Shuai Han ◽  
Ge Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Heterochromatin Protein 1 ◽  
Self Renewal ◽  
Blastema Formation ◽  
Cell Fate Decisions ◽  
Chromatin Regulators

Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED–HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration.

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