Germ cells commit somatic stem cells to differentiation following priming by PI3K/Tor activity in the Drosophila testis

How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline.

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Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

10.1101/2021.01.12.426342 ◽

2021 ◽

Author(s):

Diego Sainz de la Maza ◽

Silvana Hof-Michel ◽

Lee Phillimore ◽

Christian Bökel ◽

Marc Amoyel

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cell Cycle Progression ◽

Stem Cell Differentiation ◽

Mitochondrial Activity ◽

Self Renewal ◽

Cycle Progression ◽

Cell Identity ◽

Drosophila Testis

AbstractStem cells maintain tissue homeostasis by proliferating to replace cells lost to damage or natural turnover. Whereas stem and progenitor cells proliferate, fully differentiated cells exit the cell cycle. How cell identity and cell cycle state are coordinated during this process is still poorly understood. The Drosophila testis niche supports germline stem cells and somatic cyst stem cells (CySCs), which are the only proliferating somatic cells in the testis. CySCs give rise to post-mitotic cyst cells and therefore provide a tractable model to ask how stem cell identity is linked to proliferation. We show that the G1/S cyclin, Cyclin E, is required for CySC self-renewal; however, its canonical transcriptional regulator, a complex of the E2f1 and Dp transcription factors is dispensable for self-renewal and cell cycle progression. Nevertheless, we demonstrate that E2f1/Dp activity must be silenced to allow CySCs to differentiate. We show that E2f1/Dp activity inhibits the expression of genes important for mitochondrial activity. Furthermore, promoting mitochondrial activity or biogenesis is sufficient to rescue the differentiation of CySCs with ectopic E2f1/Dp activity but not their exit from the cell cycle. Our findings together indicate that E2f1/Dp coordinates cell cycle progression with stem cell identity by regulating the metabolic state of CySCs.

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punt and schnurri regulate a somatically derived signal that restricts proliferation of committed progenitors in the germline

Development ◽

10.1242/dev.124.21.4383 ◽

1997 ◽

Vol 124 (21) ◽

pp. 4383-4391 ◽

Cited By ~ 8

Author(s):

E. Matunis ◽

J. Tran ◽

P. Gonczy ◽

K. Caldwell ◽

S. DiNardo

Keyword(s):

Stem Cell ◽

Germ Cells ◽

Cell Lineage ◽

Germline Stem Cell ◽

Tgf Beta ◽

Signal Transducers ◽

Daughter Cells ◽

Stem Cell Lineage ◽

Mosaic Analysis ◽

Cyst Cells

To identify regulators of stem cell lineages, we are focusing on spermatogenesis in Drosophila. In spermatogenesis, each germline stem cell divides asymmetrically, renewing itself and producing a transiently amplifying daughter, which divides four times. By screening for mutants in which daughter cells fail to stop dividing, we find that the TGF-beta signal transducers schnurri and punt are required to limit transient amplification of germ cells. Mosaic analysis demonstrates that punt and schnurri act within somatic cyst cells that surround germ cells, rather than in germ cells. Thus, a cyst-cell-derived signal restricts germ cell proliferation and this signal is initiated by input from a member of the TGF-beta superfamily. Thus, a signal relay regulates progression through the germline stem cell lineage.

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Innate immune signalling drives loser cell elimination during stem cell competition in the Drosophila testis

10.1101/2020.03.05.979161 ◽

2020 ◽

Cited By ~ 1

Author(s):

Silvana Hof-Michel ◽

Ljubinka Cigoja ◽

Sabina Huhn ◽

Christian Bökel

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Innate Immune ◽

Cell Competition ◽

Cell Behaviour ◽

Cell Clones ◽

Cyst Cells ◽

Drosophila Testis ◽

Fate Decision

AbstractIn the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for the surrounding germline and somatic stem cells. Stem cells of both populations compete for physical retention in the niche, and stem cell clones unable to transduce any one niche signal are rapidly eliminated by differentiation. We have recently mapped the transcriptomes of isolated somatic cyst stem cells and differentiated cyst cells, and found that the stem cells but not their differentiated progeny activate an immune response involving the NF-κB transcription factor Relish (Rel).Here we show i) that Rel activation is not required for stemness but occurs physiologically in “losers” of stem cell competition, ii) that loss of Rel or the upstream receptor Toll suppresses loser elimination irrespective of how loser fate was induced, and iii) that clonal Rel activation is sufficient for the displacent of neutral or winner cells from the niche, even if the winners otherwise retain stem cell properties.This generalized mechanism for the elimination of “loser” stem cells may mask the compound nature of stem cell behaviour, and instead generate the impression of a binary cell fate decision between stemness and differentiation.

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Asymmetric cell division of mammary stem cells

Cell Division ◽

10.1186/s13008-021-00073-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shaan N. Chhabra ◽

Brian W. Booth

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cell Division ◽

Asymmetric Cell Division ◽

Mammary Stem Cells ◽

Self Renewal ◽

Symmetric Division ◽

Daughter Cells ◽

Mammary Stem

AbstractSomatic stem cells are distinguished by their capacity to regenerate themselves and also to produce daughter cells that will differentiate. Self-renewal is achieved through the process of asymmetric cell division which helps to sustain tissue morphogenesis as well as maintain homeostasis. Asymmetric cell division results in the development of two daughter cells with different fates after a single mitosis. Only one daughter cell maintains “stemness” while the other differentiates and achieves a non-stem cell fate. Stem cells also have the capacity to undergo symmetric division of cells that results in the development of two daughter cells which are identical. Symmetric division results in the expansion of the stem cell population. Imbalances and deregulations in these processes can result in diseases such as cancer. Adult mammary stem cells (MaSCs) are a group of cells that play a critical role in the expansion of the mammary gland during puberty and any subsequent pregnancies. Furthermore, given the relatively long lifespans and their capability to undergo self-renewal, adult stem cells have been suggested as ideal candidates for transformation events that lead to the development of cancer. With the possibility that MaSCs can act as the source cells for distinct breast cancer types; understanding their regulation is an important field of research. In this review, we discuss asymmetric cell division in breast/mammary stem cells and implications on further research. We focus on the background history of asymmetric cell division, asymmetric cell division monitoring techniques, identified molecular mechanisms of asymmetric stem cell division, and the role asymmetric cell division may play in breast cancer.

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Faculty Opinions recommendation of Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046511.793510489 ◽

2015 ◽

Author(s):

Nina Drize

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Cell Compartment ◽

Self Renewal ◽

Hematopoietic Stem ◽

Stem Cell Compartment

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Faculty Opinions recommendation of Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046511.519860 ◽

2007 ◽

Author(s):

Gay Crooks

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Cell Compartment ◽

Self Renewal ◽

Hematopoietic Stem ◽

Stem Cell Compartment

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Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666181002151330 ◽

2019 ◽

Vol 14 (5) ◽

pp. 428-436 ◽

Cited By ~ 4

Author(s):

Gabriele D. Bigoni-Ordóñez ◽

Daniel Czarnowski ◽

Tyler Parsons ◽

Gerard J. Madlambayan ◽

Luis G. Villa-Diaz

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

The Self ◽

Self Renewal ◽

Terminal Disease

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

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Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200512105347 ◽

2020 ◽

Vol 15 (6) ◽

pp. 531-546 ◽

Cited By ~ 1

Author(s):

Hwa-Yong Lee ◽

In-Sun Hong

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Oxidative Phosphorylation ◽

Metabolic Pathways ◽

Critical Role ◽

The Self ◽

Specific Cell ◽

Differentiation Potential ◽

Self Renewal ◽

Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

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Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200309145901 ◽

2020 ◽

Vol 15 ◽

Author(s):

Nese Unver

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Immune Cells ◽

Tumor Recurrence ◽

Inflammatory Factors ◽

Cancer Stemness ◽

Self Renewal ◽

Inflammatory Stress ◽

Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

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