scholarly journals Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans

2015 ◽  
Vol 112 (3) ◽  
pp. E287-E296 ◽  
Author(s):  
Omid F. Harandi ◽  
Victor R. Ambros
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Developmental Disorders ◽  
Developmental Timing ◽  
Cell Lineages ◽  
Stem Cell Maintenance ◽  
Seam Cell ◽  
Cellular Asymmetry ◽  
Evolutionarily Conserved ◽  
Posterior Pharynx

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms underlying stage-specific transitions between self-renewing and proliferative behavior in the seam cell lineages. We show that mutations of genes in the heterochronic developmental timing pathway, including lin-14 (lineage defect), lin-28, lin-46, and the lin-4 and let-7 (lethal defects)-family microRNAs, affect the activity of LIT-1/POP-1 cellular asymmetry machinery and APR-1 polarity during larval development. Surprisingly, heterochronic mutations that enhance LIT-1 activity in seam cells can simultaneously also enhance the opposing, POP-1 activity, suggesting a role in modulating the potency of the cellular polarizing activity of the LIT-1/POP-1 system as development proceeds. These findings illuminate how the evolutionarily conserved cellular asymmetry machinery can be coupled to microRNA-regulated developmental pathways for robust regulation of stem cell maintenance and proliferation during the course of development. Such genetic interactions between developmental timing regulators and cell polarity regulators could underlie transitions between asymmetric and symmetric stem cell fates in other systems and could be deregulated in the context of developmental disorders and cancer.

scholarly journals A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sneha L. Koneru ◽  
Fu Xiang Quah ◽  
Ritobrata Ghose ◽  
Mark Hintze ◽  
Nicola Gritti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Single Molecule ◽  
Phenotypic Variability ◽  
Low Frequency ◽  
Time Lapse ◽  
Cell Number ◽  
Seam Cell ◽  
Neuronal Tissues

AbstractDevelopmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

The demise of the Platonic worm

Nematology ◽  
2000 ◽  
Vol 2 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Armand Leroi ◽  
Scott Emmons ◽  
Ana Cunha ◽  
Ricardo B.R. Azevedo
Keyword(s):  
Caenorhabditis Elegans ◽  
Nematode Species ◽  
Cell Number ◽  
Cell Lineages ◽  
Panagrellus Redivivus ◽  
Seam Cell ◽  
Nous Montrons ◽  
Adult Cell ◽  
Free Living Nematode ◽  
Nuclear Number

AbstractNematodes are generally considered to have an adult cell number that does not vary among wildtype individuals as a consequence of invariant cell lineages (eutely). However, there is extensive evidence that at least some cell lineages can be variable in nematodes. In a comparative study of 13 free-living nematode species, we have shown that the adult epidermis of most species contained variable numbers of nuclei and that this variance was positively correlated with mean epidermal nuclear number. Here we present simulations of the lateral seam cell lineages of four species and show that variance in cell number is influenced by lineage topology, as well as by the frequency of lineage variants. We show that the epidermal variability of Panagrellus redivivus cannot be accounted for by the complexity of its lineage, but requires higher levels of lineage variability than are found in Caenorhabditis elegans, Oscheius myriophila and Rhabditella octopleura. Our findings suggest that many nematodes may have tissues composed of indeterminate numbers of cells formed from variable lineages and, as such, resemble other metazoans. Les nématodes sont généralement considérés comme ayant un nombre de cellules invariable chez les individus de type sauvage, conséquence d’un lignage cellulaire fixe (eutélie). Cependant, il est d’évidence qu’au moins certains des lignages cellulaires peuvent varier chez les nématodes. Dans une étude comparative portant sur 13 espèces de nématodes libres, nous avions montré que l’épiderme de la plupart de ces espèces comportait un nombre variable de noyaux et que cette variabilité était corrélée positivement avec le nombre de noyaux épidermiques. Nous présentons ici des simulations des lignages cellulaires de la suture latérale de quatre espèces et démontrons que le nombre de cellules est influencé tant par la topologie du lignage que par la fréquence des variants de ce lignage. Nous montrons que la variabilité de l’épiderme de Panagrellus redivivus ne peut être mise au compte de la complexité de son lignage, mais demande des niveaux élevés de variabilité de ce lignage, tels ceux trouvés chez Caenorhabditis elegans, Oscheius myriophila et Rhabditella octopleura. Nos observations suggèrent que nombre de nématodes possèdent des tissus composés d’un nombre indéterminé de cellules dérivant de lignages variables et, de ce fait, ressemblent aux autres metazoaires.

scholarly journals Cytokinin-CLAVATA crosstalk is an ancient mechanism regulating shoot meristem homeostasis in land plants

2021 ◽  
Author(s):  
Adrienne HK Roeder ◽  
Michael J Scanlon ◽  
Joseph Cammarata ◽  
Christopher Morales Farfan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Flowering Plant ◽  
Shoot Meristem ◽  
Cytokinin Signaling ◽  
Cytokinin Receptor ◽  
Stem Cell Maintenance ◽  
Stem Cell Regulation ◽  
Evolutionarily Conserved ◽  
Cell Organization

Plant shoots grow from stem cells within Shoot Apical Meristems (SAMs), which produce lateral organs while maintaining the stem cell pool. In the model flowering plant Arabidopsis, the CLAVATA (CLV) pathway functions antagonistically with cytokinin signaling to control the size of the multicellular SAM via negative regulation of the stem cell organizer WUSCHEL (WUS). Although comprising just a single cell, the SAM of the model moss Physcomitrium patens (formerly Physcomitrella) performs equivalent functions during stem cell maintenance and organogenesis, despite the absence of WUS-mediated stem cell organization. Our previous work showed that the stem cell-delimiting function of the CLV pathway receptors CLAVATA1 (CLV1) and RECEPTOR-LIKE PROTEIN KINASE2 (RPK2) is conserved in the moss P. patens. Here, we use P. patens to assess whether CLV-cytokinin crosstalk is also an evolutionarily conserved feature of stem cell regulation. Genetic analyses reveal that CLV1 and RPK2 regulate SAM proliferation via separate pathways in moss. Surprisingly, cytokinin receptor mutants also form ectopic stem cells in the absence of cytokinin signaling. Through modeling, we identified regulatory network archtectures that recapitulated the stem cell phenotypes of clv1 and rpk2 mutants, cytokinin application, cytokinin receptor mutations, and higher-order combinations of these perturbations. These models predict that CLV1 and RPK2 act through separate pathways wherein CLV1 represses cytokinin-mediated stem cell initiation and RPK2 inhibits this process via a separate, cytokinin-independent pathway. Our analysis suggests that crosstalk between CLV1 and cytokinin signaling is an evolutionarily conserved feature of SAM homeostasis that preceded the role of WUS in stem cell organization.

scholarly journals SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans

PLoS Genetics ◽  
2017 ◽  
Vol 13 (12) ◽  
pp. e1007121 ◽  
Author(s):  
Heaji Shin ◽  
Kimberly A. Haupt ◽  
Aaron M. Kershner ◽  
Peggy Kroll-Conner ◽  
Marvin Wickens ◽  
...  
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

scholarly journals The C. elegans CBFβ homolog, BRO-1, regulates the proliferation, differentiation and specification of the stem cell-like seam cell lineages

2007 ◽  
Vol 309 (2) ◽  
pp. 259-272 ◽  
Author(s):  
Dan Xia ◽  
Yuxia Zhang ◽  
Xinxin Huang ◽  
Yinyan Sun ◽  
Hong Zhang
Keyword(s):  
Stem Cell ◽  
Cell Lineages ◽  
C Elegans ◽  
Seam Cell

scholarly journals Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hannah S Seidel ◽  
Judith Kimble
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Germline Stem Cells ◽  
Stem Cell Maintenance ◽  
M Phase ◽  
Cell Maintenance

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells—including germline stem cells—become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions—GLP-1/Notch signaling—becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

scholarly journals Sexual dimorphism of niche architecture and regulation of the Caenorhabditis elegans germline stem cell pool

2019 ◽  
Vol 30 (14) ◽  
pp. 1757-1769 ◽  
Author(s):  
Sarah L. Crittenden ◽  
ChangHwan Lee ◽  
Ipsita Mohanty ◽  
Sindhu Battula ◽  
Karla Knobel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Sexual Dimorphism ◽  
Germline Stem Cell ◽  
Molecular Response ◽  
Sexually Dimorphic ◽  
Stem Cell Maintenance ◽  
Cell Pool ◽  
Cell Niche ◽  
Stem Cell Pool

Stem cell maintenance by niche signaling is a common theme across phylogeny. In the Caenorhabditis elegans gonad, the broad outlines of germline stem cell (GSC) regulation are the same for both sexes: GLP-1/Notch signaling from the mesenchymal distal tip cell niche maintains GSCs in the distal gonad of both sexes and does so via two key stem cell regulators, SYGL-1 and LST-1. Yet most recent analyses of niche signaling and GSC regulation have focused on XX hermaphrodites, an essentially female sex making sperm in larvae and oocytes in adults. Here we focus on GSC regulation in XO males. Sexual dimorphism of niche architecture, reported previously, suggested that the molecular responses to niche signaling or numbers of GSCs might also be sexually distinct. Remarkably, this is not the case. This work extends our understanding of the sexually dimorphic niche architecture, but also demonstrates that the dimorphic niches drive a similar molecular response and maintain a similar number of GSCs in their stem cell pools.

scholarly journals Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

2018 ◽  
Author(s):  
Eva Zacharioudaki ◽  
Julia Falo Sanjuan ◽  
Sarah Bray
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Target Gene ◽  
Notch Signalling ◽  
Normal Process ◽  
Nurd Complex ◽  
Cell Lineages ◽  
Stem Cell Maintenance ◽  
Cell Maintenance ◽  
Mitogenic Signal

AbstractTo progress towards differentiation, the progeny of stem cells need to extinguish expression of stem cell maintenance genes. Failures in these mechanisms that suppress stem cell programmes can lead to supernumerary stem cells and drive tumorigenesis. In Drosophila neural stem cell lineages, excessive Notch signalling results in supernumerary stem cells causing hyperplasia. But the onset of hyperplasia is considerably delayed implying there are mechanisms that resist the mitogenic signal. Monitoring live the expression of an early NSC marker, the Notch target gene E(spl)mγ, revealed that the normal process of NSC fate attenuation is still initiated even in the presence of excess Notch activity so that the re-emergence of stem cell properties occurs only in older progeny. Screening for factors responsible, we found that depletion of Mi-2 and other members of the NuRD ATP remodeling complex dramatically enhanced the Notch-induced hyperplasia. Under these conditions, E(spl)mγ was no longer extinguished in the stem cell progeny, but instead remained at high levels. We propose that Mi-2 is required for decommissioning stem cell enhancers in their progeny, enabling the switch towards a more differentiated fate and rendering them insensitive to mitogenic factors such as Notch.

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