Drosophila Stem Cell Niches: A Decade of Discovery Suggests a Unified View of Stem Cell Regulation

Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Developmental Cell (Impact Factor: 9.71). 07/2011; 21(1):159-71. DOI: 10.1016/j.devcel.2011.06.018
Source: PubMed


The past decade of research on Drosophila stem cells and niches has provided key insights. Fly stem cells do not occupy a special "state" based on novel "stem cell genes" but resemble transiently arrested tissue progenitors. Moreover, individual stem cells and downstream progenitors are highly dynamic and dispensable, not tissue bulwarks. Niches, rather than fixed cell lineages, ensure tissue health by holding stem cells and repressing cell differentiation inside, but not outside. We review the five best-understood adult Drosophila stem cells and argue that the fundamental biology of stem cells and niches is conserved between Drosophila and mice.

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Available from: Vicki Losick, Oct 22, 2015
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    • "Developmentally all stem cells need to be tightly regulated as uncontrolled differentiation leads to rapid depletion of stem cells, whereas uncontrolled self-renewal leads to an excess of stem cells resembling tumorigenesis. Thus, there are series of intricate genetic pathways that assure the initiation of correct self-renewal and differentiation after each stem cell division (Doe 2008; Losick et al. 2011; Spradling et al. 2011; Lehmann 2012). Most mutations occurring across the genes that control the stem cell development are then predicted to be strongly deleterious, as perturbations would cause sterility or lethality. "
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    ABSTRACT: Here, we study the molecular evolution of a near complete set of genes that had functional evidence in the regulation of the Drosophila germline and neural stem cell. Some of these genes have previously been shown to be rapidly evolving by positive selection raising the possibility that stem cell genes as a group have elevated signatures of positive selection. Using recent Drosophila comparative genome sequences and population genomic sequences of Drosophila melanogaster, we have investigated both long- and short-term evolution occurring across these two different stem cell systems, and compared them with a carefully chosen random set of genes to represent the background rate of evolution. Our results showed an excess of genes with evidence of a recent selective sweep in both germline and neural stem cells in D. melanogaster. However compared with their control genes, both stem cell systems had no significant excess of genes with long-term recurrent positive selection in D. melanogaster, or across orthologous sequences from the melanogaster group. The evidence of long-term positive selection was limited to a subset of genes with specific functions in both the germline and neural stem cell system.
    Full-text · Article · Oct 2015 · Genome Biology and Evolution
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    • "The GSC niche itself is made of a group of five to seven cap cells positioned at the tip of the germarium, contacting the terminal filament cells anteriorly and anchoring GSCs posteriorly through DE-cadherin-b-catenin-mediated adhesion (Song et al., 2002). Cap cells produce the decapentaplegic (Dpp)/BMP ligand to maintain the GSC pool (Chen and McKearin, 2003; Guo and Wang, 2009; Harris and Ashe, 2011; Losick et al., 2011; Xie and Spradling, 1998). The ECM in Drosophila essentially consists of basement membrane (BM), aka basal lamina (Fessler and Fessler, 1989). "
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    ABSTRACT: The extracellular matrix plays an essential role for stem cell differentiation and niche homeostasis. Yet, the origin and mechanism of assembly of the stem cell niche microenvironment remain poorly characterized. Here, we uncover an association between the niche and blood cells, leading to the formation of the Drosophila ovarian germline stem cell niche basement membrane. We identify a distinct pool of plasmatocytes tightly associated with the developing ovaries from larval stages onward. Expressing tagged collagen IV tissue specifically, we show that the germline stem cell niche basement membrane is produced by these "companion plasmatocytes" in the larval gonad and persists throughout adulthood, including the reproductive period. Eliminating companion plasmatocytes or specifically blocking their collagen IV expression during larval stages results in abnormal adult niches with excess stem cells, a phenotype due to aberrant BMP signaling. Thus, local interactions between the niche and blood cells during gonad development are essential for adult germline stem cell niche microenvironment assembly and homeostasis.
    Full-text · Article · Oct 2015 · Cell Reports
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    • "Stem cells have two important properties, self-renewal and differentiation, which are critical for continuously generating new functional cells to maintain tissue homeostasis. The self-renewal property is controlled in various stem cell systems by interplays between signals from the niche and intrinsic factors (Li and Xie, 2005; Morrison and Spradling, 2008; Losick et al., 2011). Germ line stem cells (GSCs) in the Drosophila ovary and testis are attractive systems for studying stem cell selfrenewal at the molecular and cellular level (Fuller and Spradling, 2007; Xie, 2013). "
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    ABSTRACT: eLife digest An animal or plant has many different types of cells that have specific roles in the life of the organism. These cells are organized into tissues. In most tissues in adult animals, small groups of cells called stem cells are responsible for replacing the other cells that have been lost due to disease, injury, or as part of normal body maintenance. The ‘germ line’ stem cells of female fruit flies—which produce female sex cells (or eggs)—are an effective system for studying how stem cells are regulated. These cells live in an area of the ovary called a stem cell niche. Each time a stem cell divides, it produces one stem cell and one other daughter cell. This daughter cell then moves into another niche called the ‘differentiation’ niche and undergoes a series of divisions that produce the egg cells. The differentiation niche is formed by escort cells and is crucial for producing the egg cells, but it is not clear how the escort cells promote this process, or how the niche is maintained. Wang et al. have now studied the differentiation niche in more detail. The experiments show that a cell communication system called Wnt signaling maintains the differentiation niche by controlling the ability of the escort cells to grow and divide. If Wnt signaling is defective, the differentiation niche is lost, which disrupts the formation of egg cells. Further experiments show that two proteins called Wnt2 and Wnt4 in the differentiation niche—which activate Wnt signaling—act as signals to regulate the niche, mainly by controlling the expression of four particular genes. These four genes encode enzymes that remove ‘reactive oxygen species’ from cells. Wang et al.'s findings have revealed an important role for Wnt signaling in maintaining the differentiation niche. The next step is to figure out the details of how this works. DOI:
    Full-text · Article · Oct 2015 · eLife Sciences
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