scholarly journals Asymmetric nuclear division of neural stem cells contributes to the formation of sibling nuclei with different identities

2020 ◽  
Author(s):  
Chantal Roubinet ◽  
Ian J. White ◽  
Buzz Baum

AbstractCellular diversity in multicellular organisms is often generated via asymmetric divisions. In the fly, for example, neural stem cells divide asymmetrically to generate a large self-renewing stem cell and a smaller sibling that differentiates. Efforts to understand how these different cell fates are generated have focused on the asymmetric segregation of cortically-localised transcription factors at division, which preferentially enter single daughter cell nuclei to change their fate. However, we find that the nuclear compartment in these cells remains intact throughout mitosis and is asymmetrically inherited, giving rise to sibling nuclei that differ profoundly in size, envelope composition and fate markers. These data reveal the importance of considering nuclear remodelling during stem cell divisions, and show how daughter cell fates depend on the coordination of the asymmetric inheritance of cortical fate markers with asymmetric nuclear division.

2017 ◽  
Author(s):  
Kailin R. Mesa ◽  
Kyogo Kawaguchi ◽  
David G. Gonzalez ◽  
Katie Cockburn ◽  
Jonathan Boucher ◽  
...  

Many adult tissues are dynamically sustained by the rapid turnover of stem cells. Yet, how cell fates such as self-renewal and differentiation are orchestrated to achieve long-term homeostasis remains elusive. Studies utilizing clonal tracing experiments in multiple tissues have argued that while stem cell fate is balanced at the population level, individual cell fate - to divide or differentiate – is determined intrinsically by each cell seemingly at random ( 1 2 3 4 5). These studies leave open the question of how cell fates are regulated to achieve fate balance across the tissue. Stem cell fate choices could be made autonomously by each cell throughout the tissue or be the result of cell coordination ( 6 7). Here we developed a novel live tracking strategy that allowed recording of every division and differentiation event within a region of epidermis for a week. These measurements reveal that stem cell fates are not autonomous. Rather, direct neighbors undergo coupled opposite fate decisions. We further found a clear ordering of events, with self-renewal triggered by neighbor differentiation, but not vice-versa. Typically, around 1-2 days after cell delamination, a neighboring cell entered S/G2 phase and divided. Functional blocking of this local feedback showed that differentiation continues to occur in the absence of cell division, resulting in a rapid depletion of the epidermal stem cell pool. We thus demonstrate that the epidermis is maintained by nearest neighbor coordination of cell fates, rather than by asymmetric divisions or fine-tuned cell-autonomous stochastic fate choices. These findings establish differentiation-dependent division as a core feature of homeostatic control, and define the relevant time and length scales over which homeostasis is enforced in epithelial tissues.


2021 ◽  
Author(s):  
Julie Ray ◽  
Keith A. Maggert

Mitotically-stable epigenetic memory requires a mechanism for the maintenance of gene-regulatory information through the cell division cycle. Typically DNA-protein contacts are disrupted by DNA replication, but in some cases locus- specific association between DNA and overlying histones may appear to be maintained, providing a plausible mechanism for the transmission of histone-associated gene-regulatory information to daughter cells. Male Drosophila melanogaster testis germ stem cell divisions seem a clear example of such inheritance, as previously chromatin-bound histone H3.2 proteins (presumably with their post-translational modifications intact) have been reported to be retained in the germ stem cell nuclei, while newly synthesized histones are incorporated exclusively into daughter spermatogonial chromosomes. To investigate the rate of errors in this selective partitioning that may lead to defects in the epigenetic identity of germ stem cells, we employed a photoswitchable Dendra2 moiety as a C-terminal fusion on Histones H3; we could thereby discriminate histones translated before photoswitching and those translated after. We found instead that male germ line stem cell divisions show no evidence of asymmetric histone partitioning, even after a single division, and thus no evidence for locus-specific retention of either Histone H3.2 or Histone H3.3. We considered alternative hypotheses for the appearance of asymmetry and find that previous reports of asymmetric histone distribution in male germ stem cells can be satisfactorily explained by asynchrony between subsequent sister stem cell and spermatogonial divisions.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.


Stem Cells ◽  
2008 ◽  
Vol 26 (8) ◽  
pp. 2131-2141 ◽  
Author(s):  
Dengke K. Ma ◽  
Cheng-Hsuan J. Chiang ◽  
Karthikeyan Ponnusamy ◽  
Guo-li Ming ◽  
Hongjun Song

2016 ◽  
Vol 7 ◽  
pp. 926-936 ◽  
Author(s):  
Igor M Pongrac ◽  
Marina Dobrivojević ◽  
Lada Brkić Ahmed ◽  
Michal Babič ◽  
Miroslav Šlouf ◽  
...  

Background: Cell tracking is a powerful tool to understand cellular migration, dynamics, homing and function of stem cell transplants. Nanoparticles represent possible stem cell tracers, but they differ in cellular uptake and side effects. Their properties can be modified by coating with different biocompatible polymers. To test if a coating polymer, poly(L-lysine), can improve the biocompatibility of nanoparticles applied to neural stem cells, poly(L-lysine)-coated maghemite nanoparticles were prepared and characterized. We evaluated their cellular uptake, the mechanism of internalization, cytotoxicity, viability and proliferation of neural stem cells, and compared them to the commercially available dextran-coated nanomag®-D-spio nanoparticles. Results: Light microscopy of Prussian blue staining revealed a concentration-dependent intracellular uptake of iron oxide in neural stem cells. The methyl thiazolyl tetrazolium assay and the calcein acetoxymethyl ester/propidium iodide assay demonstrated that poly(L-lysine)-coated maghemite nanoparticles scored better than nanomag®-D-spio in cell labeling efficiency, viability and proliferation of neural stem cells. Cytochalasine D blocked the cellular uptake of nanoparticles indicating an actin-dependent process, such as macropinocytosis, to be the internalization mechanism for both nanoparticle types. Finally, immunocytochemistry analysis of neural stem cells after treatment with poly(L-lysine)-coated maghemite and nanomag®-D-spio nanoparticles showed that they preserve their identity as neural stem cells and their potential to differentiate into all three major neural cell types (neurons, astrocytes and oligodendrocytes). Conclusion: Improved biocompatibility and efficient cell labeling makes poly(L-lysine)-coated maghemite nanoparticles appropriate candidates for future neural stem cell in vivo tracking studies.


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