scholarly journals Wnt- and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division

2020 ◽  
Author(s):  
Sergi Junyent ◽  
Joshua Reeves ◽  
James L. A. Szczerkowski ◽  
Clare L. Garcin ◽  
Tung-Jui Trieu ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Cell Biology ◽  
Wnt Pathway ◽  
Asymmetric Cell Division ◽  
Embryonic Stem ◽  
Cell Dynamics ◽  
Pathway Activation ◽  
Wnt Ligands ◽  
Ligand Stabilization

ABSTRACTWnt signalling regulates many aspects of cell biology. Wnt-pathway activation and its downstream effects have been extensively studied, but the dynamic analysis of Wnt-ligands on mammalian cellular membranes is obstructed by difficulties of visualization. We overcome this using microbead-tethered Wnts presented to single embryonic stem cells, which undergo Wnt-mediated asymmetric cell division (ACD). Through live imaging and genetic editing, we show that knockout of Wnt co-receptor Lrp5 promotes cytoneme formation and Wnt-recruitment, which requires Lrp6 and β-catenin. Lrp5 facilitates ligand-retention at the membrane, and alongside Lrp6 mediates Wnt-ligand stabilization and positioning. β-catenin or Wnt co-receptor knockout causes misorientation at mitosis, and all but Lrp5 are required for Wnt-orientated ACD. Surprisingly, ionotropic glutamate receptor (iGluR) activity enables initial Wnt-recruitment, positioning, and ultimately oriented ACD. Uniquely, we have scrutinized the early Wnt ligand-membrane interaction, linking roles of Wnt-pathway components and crosstalk with iGluRs in guiding cell fate determination by oriented ACD.

scholarly journals Wnt-and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sergi Junyent ◽  
Joshua C Reeves ◽  
James LA Szczerkowski1 ◽  
Clare L Garcin ◽  
Tung-Jui Trieu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Glutamate Receptors ◽  
Cell Fate ◽  
Cell Biology ◽  
Wnt Pathway ◽  
Asymmetric Cell Division ◽  
Cell Signalling ◽  
Embryonic Stem ◽  
Kainate Receptors

The Wnt-pathway is part of a signalling network that regulates many aspects of cell biology. Recently we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs). Here, we demonstrate that this crosstalk persists throughout the Wnt3a-response in ESCs. Both AMPA- and Kainate-receptors regulate early Wnt3a-recruitment, dynamics on the cell membrane, and orientation of the spindle towards a Wnt3a-source at mitosis. AMPA-receptors specifically are required for segregating cell fate components during Wnt3a-mediated asymmetric cell division (ACD). Using Wnt-pathway component knockout lines, we determine that Wnt co-receptor Lrp6 has particular functionality over Lrp5 in cytoneme formation, and in facilitating ACD. Both Lrp5 and 6, alongside pathway effector β-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localized Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

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.

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.

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

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

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.

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

1998 ◽  
Vol 18 (1) ◽  
pp. 598-607 ◽  
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.

scholarly journals Plexin-B2 is a key regulator of cell mechanics during multicellular organization

2019 ◽  
Author(s):  
Chrystian Junqueira Alves ◽  
Rafael Dariolli ◽  
Theodore Hannah ◽  
Robert J. Wiener ◽  
Nicolas Daviaud ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Tissue Mechanics ◽  
Cell Stiffness ◽  
Adhesive Properties ◽  
Force Microscopy ◽  
Rac Gtpases ◽  
Tensile Forces ◽  
Tissue Geometry

SUMMARYDuring multicellular organization, individual cells need to constantly respond to environmental cues and adjust contractile and adhesive forces in order to maintain tissue integrity. The signaling pathways linking biochemical cues and tissue mechanics are unclear. Here, we show that Plexin-B2 regulates mechanochemical integration during multicellular organization. In human embryonic stem cells (hESCs), Plexin-B2 controls cell shape and tissue geometry in both 2D epithelial colony and 3D spheroid aggregates by regulating actomyosin contractility and junctional/cell-matrix adhesive properties. Atomic force microscopy (AFM) directly demonstrates that Plexin-B2 modulates cell stiffness in hESC colonies, which in turn impacts cell proliferation and cell fate specification through β-catenin signaling and YAP mechanosensing. YAP also functions as a mechanoregulator downstream of Plexin-B2, thus forming a mechanochemical integrative loop. In human neuroprogenitor cells (hNPCs), Plexin-B2 similarly controls cell stiffness and tensile forces, as revealed by AFM and FRET tension sensor studies. Strikingly, Plexin-B2-deficient hNPCs display accelerated neuronal differentiation. From an organogenesis perspective, Plexin-B2 maintains cytoarchitectural integrity of neuroepithelium, as modeled in cerebral organoids. On a signaling level, Plexin-B2 engages extracellular as well as intracellular Ras-GAP and RBD domains for mechanoregulation through Rap and Rac GTPases. Our data unveil a fundamental function of Plexin-B2 for mechanochemical integration during multicellular organization, and shed light on the principle of force-mediated regulation of stem cell biology and tissue morphogenesis.

scholarly journals Mathematical modeling of plant cell fate transitions controlled by hormonal signals

2019 ◽  
Author(s):  
Filip Z. Klawe ◽  
Thomas Stiehl ◽  
Peter Bastian ◽  
Christophe Gaillochet ◽  
Jan U. Lohmann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cell Division ◽  
Cell Fate ◽  
Plant Architecture ◽  
Two Dimensional ◽  
Cell Dynamics ◽  
Non Linear

AbstractCoordination of fate transition and cell division is crucial to maintain the plant architecture and to achieve efficient production of plant organs. In this paper, we analysed the stem cell dynamics at the shoot apical meristem (SAM) that is one of the plant stem cells locations. We designed a mathematical model to elucidate the impact of hormonal signaling on the fate transition rates between different zones corresponding to slowly dividing stem cells and fast dividing transit amplifying cells. The model is based on a simplified two-dimensional disc geometry of the SAM and accounts for a continuous displacement towards the periphery of cells produced in the central zone. Coupling growth and hormonal signaling results in a non-linear system of reaction-diffusion equations on a growing domain with the growth velocity depending on the model components. The model is tested by simulating perturbations in the level of key transcription factors that maintain SAM homeostasis. The model provides new insights on how the transcription factor HECATE is integrated in the regulatory network that governs stem cell differentiation.SummaryPlants continuously generate new organs such as leaves, roots and flowers. This process is driven by stem cells which are located in specialized regions, so-called meristems. Dividing stem cells give rise to offspring that, during a process referred to as cell fate transition, become more specialized and give rise to organs. Plant architecture and crop yield crucially depend on the regulation of meristem dynamics. To better understand this regulation, we develop a computational model of the shoot meristem. The model describes the meristem as a two-dimensional disk that can grow and shrink over time, depending on the concentrations of the signalling factors in its interior. This allows studying how the non-linear interaction of multiple transcription factors is linked to cell division and fate-transition. We test the model by simulating perturbations of meristem signals and comparing them to experimental data. The model allows simulating different hypotheses about signal effects. Based on the model we study the specific role of the transcription factor HECATE and provide new insights in its action on cell dynamics and in its interrelation with other known transcription factors in the meristem.

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

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.

Sign in / Sign up

Export Citation Format

Share Document