The Significant Role of Centrosomes in Stem Cell Division and Differentiation

2011 ◽  
Vol 17 (4) ◽  
pp. 506-512 ◽  
Author(s):  
Heide Schatten ◽  
Qing-Yuan Sun

AbstractThe role of centrosomes in stem cell division has recently been highlighted and further ascribes important functions to centrosomes in stem cell maintenance, cellular differentiation, and development. Advanced cell and molecular studies coupled with immunofluorescence, electron microscopy, and live cell imaging of specific centrosome proteins have contributed greatly to our knowledge of centrosome composition, structure, and dynamics and have uncovered new insights into mechanisms of centrosome functions in asymmetric cell division. The establishment of asymmetry and differential positioning of mother and daughter centrosomes during stem cell mitosis is important for allowing one cell to maintain stem cell characteristics while the sibling cell undergoes differentiation. Another key role for centrosomes has been revealed in primary cilia of embryonic stem cells that play significant roles in cellular signaling and are therefore critically important for stem cell decisions. Studies of signaling through primary cilia may contribute important information that may aid in the production of specific cells that are suitable for tissue repair and regeneration in the field of regenerative medicine.

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Cuie Chen ◽  
Mayu Inaba ◽  
Zsolt G Venkei ◽  
Yukiko M Yamashita

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.


2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3811
Author(s):  
M. Angeles Juanes

Intestinal epithelium architecture is sustained by stem cell division. In principle, stem cells can divide symmetrically to generate two identical copies of themselves or asymmetrically to sustain tissue renewal in a balanced manner. The choice between the two helps preserve stem cell and progeny pools and is crucial for tissue homeostasis. Control of spindle orientation is a prime contributor to the specification of symmetric versus asymmetric cell division. Competition for space within the niche may be another factor limiting the stem cell pool. An integrative view of the multiple links between intracellular and extracellular signals and molecular determinants at play remains a challenge. One outstanding question is the precise molecular roles of the tumour suppressor Adenomatous polyposis coli (APC) for sustaining gut homeostasis through its respective functions as a cytoskeletal hub and a down regulator in Wnt signalling. Here, we review our current understanding of APC inherent activities and partners in order to explore novel avenues by which APC may act as a gatekeeper in colorectal cancer and as a therapeutic target.


Author(s):  
Gerrit Beemster ◽  
Stijn Dhondt ◽  
Frederik Coppens ◽  
Roeland Merks ◽  
Dirk Inze ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Bharathi Suresh ◽  
Junwon Lee ◽  
Kye-Seong Kim ◽  
Suresh Ramakrishna

Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming.


2011 ◽  
Vol 356 (1) ◽  
pp. 215-216
Author(s):  
Kimberly A. Johnson ◽  
Chelsea Moriarty ◽  
Alissa Ortman ◽  
Rebecca Bernardos ◽  
Kim Chi Ngo ◽  
...  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sergi Junyent ◽  
Joshua C Reeves ◽  
James LA Szczerkowski1 ◽  
Clare L Garcin ◽  
Tung-Jui Trieu ◽  
...  

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.


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