A new role of Klumpfuss in establishing cell fate during the GMC asymmetric cell division

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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Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽

10.1182/blood.2020009778 ◽

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.

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

Acta Biomaterialia ◽

10.1016/j.actbio.2020.10.030 ◽

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

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

eLife ◽

10.7554/elife.33685 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 8

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.

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Who begets whom? Plant cell fate determination by asymmetric cell division

Current Opinion in Plant Biology ◽

10.1016/j.pbi.2007.11.001 ◽

2008 ◽

Vol 11 (1) ◽

pp. 34-41 ◽

Cited By ~ 26

Author(s):

Colette A ten Hove ◽

Renze Heidstra

Keyword(s):

Cell Division ◽

Cell Fate ◽

Plant Cell ◽

Asymmetric Cell Division ◽

Cell Fate Determination ◽

Fate Determination

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Regulation of the meiotic divisions of mammalian oocytes and eggs

Biochemical Society Transactions ◽

10.1042/bst20170493 ◽

2018 ◽

Vol 46 (4) ◽

pp. 797-806 ◽

Cited By ~ 10

Author(s):

Jessica R. Sanders ◽

Keith T. Jones

Keyword(s):

Cell Division ◽

Luteinizing Hormone ◽

Spindle Assembly Checkpoint ◽

Asymmetric Cell Division ◽

Homologous Chromosomes ◽

Mammalian Oocyte ◽

Cellular Events ◽

The Hours ◽

Meiosis I

Initiated by luteinizing hormone and finalized by the fertilizing sperm, the mammalian oocyte completes its two meiotic divisions. The first division occurs in the mature Graafian follicle during the hours preceding ovulation and culminates in an extreme asymmetric cell division and the segregation of the two pairs of homologous chromosomes. The newly created mature egg rearrests at metaphase of the second meiotic division prior to ovulation and only completes meiosis following a Ca2+ signal initiated by the sperm at gamete fusion. Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. In meiosis II, we examine how the egg achieves its arrest and how the fertilization Ca2+ signal allows the initiation of embryo development.

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Asymmetric cell division and differentiation; fern spore germination as a model. II. Ultrastructural studies

Proceedings of the Royal Society of Edinburgh Section B Biological Sciences ◽

10.1017/s0269727000008162 ◽

1985 ◽

Vol 86 ◽

pp. 227-230

Author(s):

Alix R. Bassel

Keyword(s):

Cell Division ◽

Metal Binding ◽

Asymmetric Cell Division ◽

Red Light ◽

Nuclear Migration ◽

Silver Stain ◽

Metal Binding Sites ◽

Ultrastructural Studies ◽

Fern Spore Germination

SynopsisThe germination of Onoclea spores is a model system with many advantages for the study of asymmetric cell division and cellular differentiation. Our results suggest that both microtubules and a lipophilic site are important in the nuclear migration to one end of the spore prior to asymmetric cell division. A metalbinding region containing pore-like structures in the proximal face of the spore coat may be a source of the inherent polarity of the spore. The pattern of endogenous metal binding during germination has been characterised using a sulphide-silver stain. Metal-binding sites are described in a differentiating system in which polarity is imposed externally using polarised red light. The possibility of a role of ion gradients in determining the direction of nuclear migration is discussed.

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The role of asymmetric cell division in pteridophyte cell differentiation. I. Localized metal accumulation and differentiation inVittaria gemmae andOnoclea prothallia

PROTOPLASMA ◽

10.1007/bf01276357 ◽

1987 ◽

Vol 136 (2-3) ◽

pp. 81-95 ◽

Cited By ~ 7

Author(s):

J. L. Kotenko ◽

J. H. Miller ◽

A. I. Robinson

Keyword(s):

Cell Division ◽

Cell Differentiation ◽

Asymmetric Cell Division ◽

Metal Accumulation

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Numb-Associated Kinase Interacts with the Phosphotyrosine Binding Domain of Numb and Antagonizes the Function of Numb In Vivo

Molecular and Cellular Biology ◽

10.1128/mcb.18.1.598 ◽

1998 ◽

Vol 18 (1) ◽

pp. 598-607 ◽

Cited By ~ 56

Author(s):

Cheng-ting Chien ◽

Shuwen Wang ◽

Michael Rothenberg ◽

Lily Y. Jan ◽

Yuh Nung Jan

Keyword(s):

Cell Division ◽

Cell Fate ◽

Asymmetric Cell Division ◽

Gene Dosage ◽

Specific Protein ◽

Physical Interaction ◽

Protein Protein Interaction ◽

Phosphotyrosine Binding Domain ◽

Ptb Domain

ABSTRACT During asymmetric cell division, the membrane-associated Numb protein localizes to a crescent in the mitotic progenitor and is segregated predominantly to one of the two daughter cells. We have identified a putative serine/threonine kinase, Numb-associated kinase (Nak), which interacts physically with the phosphotyrosine binding (PTB) domain of Numb. The PTB domains of Shc and insulin receptor substrate bind to an NPXY motif which is not present in the region of Nak that interacts with Numb PTB domain. We found that the Numb PTB domain but not the Shc PTB domain interacts with Nak through a peptide of 11 amino acids, implicating a novel and specific protein-protein interaction. Overexpression of Nak in the sensory organs causes both daughters of a normally asymmetric cell division to adopt the same cell fate, a transformation similar to the loss of numb function phenotype and opposite the cell fate transformation caused by overexpression of Numb. The frequency of cell fate transformation is sensitive to the numb gene dosage, as expected from the physical interaction between Nak and Numb. These findings indicate that Nak may play a role in cell fate determination during asymmetric cell divisions.

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Endodermal differentiation is reconstructed by coordination of two parallel signaling systems derived from the stele in roots

10.1101/210872 ◽

2017 ◽

Author(s):

Pengxue Li ◽

Qiaozhi Yu ◽

Chunmiao Xu ◽

Xu Gu ◽

Shilian Qi ◽

...

Keyword(s):

Cell Division ◽

Cell Fate ◽

Asymmetric Cell Division ◽

Cell Types ◽

Plant Roots ◽

Synthetic Approach ◽

Fate Map ◽

Signaling Systems ◽

Apoplastic Barrier ◽

Casparian Strips

AbstractThe plant roots represent the exquisitely controlled cell fate map in which different cell types undergo a complete status transition from stem cell division and initial fate specification, to the terminal differentiation. The endodermis is initially specified in meristem but further differentiates to form Casparian strips (CSs), the apoplastic barrier in the mature zone for the selective transport between stele and outer tissues, and thus is regarded as plant inner skin. In the Arabidopsis thaliana root the transcription factors SHORTROOT (SHR) regulate asymmetric cell division in cortical initials to separate endodermal and cortex cell layer. In this paper, we utilized synthetic approach to examine the reconstruction of fully functional Casparian strips in plant roots. Our results revealed that SHR serves as a master regulator of a hierarchical signaling cascade that, combined with stele-derived small peptides, is sufficient to rebuild the functional CS in non-endodermal cells. This is a demonstration of the deployment of two parallel signaling systems, in which both apoplastic and symplastic communication were employed, for coordinately specifying the endodermal cell fate.

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