Lox2, a putative leech segment identity gene, is expressed in the same segmental domain in different stem cell lineages

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 697-710 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
M. Shankland

The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.


2014 ◽  
Vol 23 (7) ◽  
pp. 767-778 ◽  
Author(s):  
Anouk-Martine Teichert ◽  
Schreiber Pereira ◽  
Brenda Coles ◽  
Radha Chaddah ◽  
Susan Runciman ◽  
...  




2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Daniela Drummond-Barbosa

Abstract Nutrient availability, stresses, and aging affect tissue stem cells in multicellular organisms; yet, the underlying physiological mechanisms in vivo remains largely unexplored. Dr. Drummond-Barbosa pioneered using Drosophila to study the physiology of tissue stem cell regulation. Her laboratory played a major role in delineating how diet, brain insulin-like peptides, and the TOR nutrient sensor control the germline stem cell (GSC) lineage. They also discovered that adipocyte-specific disruption of amino acid transport, other nutrient signaling, and metabolic pathways causes distinct germline phenotypes. They also showed that nuclear receptors act in multiple tissues to affect the GSC lineage through direct and indirect mechanisms. More recently, her group has been exploring how other physiological stresses affect the GSC lineage. Her group’s studies point to extensive communication between the brain, adipocytes, hepatocyte-like cells, and the germline, and underscore the complexity of the physiological network that modulates stem cell lineage behavior.



Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4361-4371 ◽  
Author(s):  
P. Gonczy ◽  
E. Matunis ◽  
S. DiNardo

Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.



eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mélanie Criqui ◽  
Aditi Qamra ◽  
Tsz Wai Chu ◽  
Monika Sharma ◽  
Julissa Tsao ◽  
...  

The precise relationship between epigenetic alterations and telomere dysfunction is still an extant question. Previously, we showed that eroded telomeres lead to differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation at pluripotency-factor promoters. Here, we uncovered that telomerase reverse transcriptase null (Tert-/-) mESCs exhibit genome-wide alterations in chromatin accessibility and gene expression during differentiation. These changes were accompanied by an increase of H3K27me3 globally, an altered chromatin landscape at the Pou5f1/Oct4 promoter, and a refractory response to differentiation cues. Inhibition of the Polycomb Repressive Complex 2 (PRC2), an H3K27 tri-methyltransferase, exacerbated the impairment in differentiation and pluripotency gene repression in Tert-/- mESCs but not wild-type mESCs, whereas inhibition of H3K27me3 demethylation led to a partial rescue of the Tert-/- phenotype. These data reveal a new interdependent relationship between H3K27me3 and telomere integrity in stem cell lineage commitment that may have implications in aging and cancer.



2009 ◽  
Vol 186 (5) ◽  
pp. 665-673 ◽  
Author(s):  
Sonia Stefanovic ◽  
Nesrine Abboud ◽  
Stéphanie Désilets ◽  
David Nury ◽  
Chad Cowan ◽  
...  

Oct4 exerts a dose-dependent dual action, as both a gatekeeper for stem cell pluripotency and in driving cells toward specific lineages. Here, we identify the molecular mechanism underlying this dual function. BMP2- or transgene-induced Oct4 up-regulation drives human embryonic and induced pluripotent stem cells to become cardiac progenitors. When embryonic stem cell pluripotency is achieved, Oct4 switches from the Sox2 to the Sox17 promoter. This switch allows the cells to turn off the pluripotency Oct4-Sox2 loop and to turn on the Sox17 promoter. This powerful process generates a subset of endoderm-expressing Sox17 and Hex, both regulators of paracrine signals for cardiogenesis (i.e., Wnt, BMP2) released into the medium surrounding colonies of embryonic stem cells. Our data thus reveal a novel molecular Oct4- and Sox17-mediated mechanism that disrupts the stem cell microenvironment favoring pluripotency to provide a novel paracrine endodermal environment in which cell lineage is determined and commits the cells to a cardiogenic fate.



2018 ◽  
Vol 115 (14) ◽  
pp. E3182-E3191 ◽  
Author(s):  
Amy Reilein ◽  
David Melamed ◽  
Simon Tavaré ◽  
Daniel Kalderon

Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space. We considered alternative mechanisms underlying population asymmetry and used quantitative modeling to predict starkly different consequences of altering proliferation rate: A variant, faster proliferating mutant stem cell should compete better only when stem cell division and differentiation are independent processes. For most types of stem cells, it has not been possible to ascertain experimentally whether division and differentiation are coupled. However, Drosophila follicle stem cells (FSCs) provided a favorable system with which to investigate population asymmetry mechanisms and also for measuring the impact of altered proliferation on competition. We found from detailed cell lineage studies that division and differentiation of an individual FSC are not coupled. We also found that FSC representation, reflecting maintenance and amplification, was highly responsive to genetic changes that altered only the rate of FSC proliferation. The FSC paradigm therefore provides definitive experimental evidence for the general principle that relative proliferation rate will always be a major determinant of competition among stem cells specifically when stem cell division and differentiation are independent.



Stem Cells ◽  
2007 ◽  
Vol 25 (5) ◽  
pp. 1090-1095 ◽  
Author(s):  
Bernard Binétruy ◽  
Lynn Heasley ◽  
Frédéric Bost ◽  
Leslie Caron ◽  
Myriam Aouadi


2021 ◽  
Vol 22 (15) ◽  
pp. 8109
Author(s):  
Wen-Yang Hu ◽  
Dan-Ping Hu ◽  
Lishi Xie ◽  
Larisa Nonn ◽  
Ranli Lu ◽  
...  

Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 (KRT13)-enriched prostate stem cells at single-cell resolution, distinguishing them from daughter progenitors. Herein, we characterized the epithelial cell lineage hierarchy in prostaspheres using single-cell RNA-seq analysis. Keratin profiling revealed three clusters of label-retaining prostate stem cells; cluster I represents quiescent stem cells (PSCA, CD36, SPINK1, and KRT13/23/80/78/4 enriched), while clusters II and III represent active stem and bipotent progenitor cells (KRT16/17/6 enriched). Gene set enrichment analysis revealed enrichment of stem and cancer-related pathways in cluster I. In non-label-retaining daughter progenitor cells, three clusters were identified; cluster IV represents basal progenitors (KRT5/14/6/16 enriched), while clusters V and VI represent early and late-stage luminal progenitors, respectively (KRT8/18/10 enriched). Furthermore, MetaCore analysis showed enrichment of the “cytoskeleton remodeling–keratin filaments” pathway in cancer stem-like cells from human prostate cancer specimens. Along with common keratins (KRT13/23/80/78/4) in normal stem cells, unique keratins (KRT10/19/6C/16) were enriched in cancer stem-like cells. Clarification of these keratin profiles in human prostate stem cell lineage hierarchy and cancer stem-like cells can facilitate the identification and therapeutic targeting of prostate cancer stem-like cells.



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