scholarly journals Comment on "Variation in cancer risk among tissues can be explained by the number of stem cell divisions"

2015 ◽  
Author(s):  
Maxime Tarabichi ◽  
Vincent Detours
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cell ◽  
Cell Division ◽  
Risk Groups ◽  
Prevention Measures ◽  
Cell Divisions ◽  
Hepatocellular Carcinomas ◽  
Major Subset ◽  
Stem Cell Divisions ◽  
Stem Cell Division

Tomasetti and Vogelstein (Science 347, 78–81, 2015) claimed that “primary prevention measures are not likely to be very effective” for many cancers because they arise mostly from random mutations fixed during stem cell division, independently of specific genetic or environmental factors. We demonstrate that their calculation for hepatocellular carcinomas overlooked a major subset of tumors proven to be preventable through vaccination. The problem, which is not limited to hepatocellular carcinoma, arises from the general reliance of their analysis on average USA incidences and the omission of incidences in specific risk groups.

scholarly journals A research note regarding "Variation in cancer risk among tissues can be explained by the number of stem cell divisions"

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2044
Author(s):  
Maxime Tarabichi ◽  
Vincent Detours
Keyword(s):  
United States ◽  
Hepatocellular Carcinoma ◽  
Stem Cell ◽  
Risk Groups ◽  
The United States ◽  
Prevention Measures ◽  
Cell Divisions ◽  
Hepatocellular Carcinomas ◽  
Major Subset ◽  
Stem Cell Divisions

Tomasetti and Vogelstein argued that 2/3 of human cancers are due to ‘bad luck’ and that “primary prevention measures [against cancer] are not likely to be very effective”. We demonstrate that their calculations for hepatocellular carcinomas overlooked a major subset of these cancers proven to be preventable through vaccination. The problem, which is not limited to hepatocellular carcinoma, arises from the general reliance of their analysis on average incidences in the United States and the omission of incidences in specific risk groups.

scholarly journals A research note regarding "Variation in cancer risk among tissues can be explained by the number of stem cell divisions"

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2044
Author(s):  
Maxime Tarabichi ◽  
Vincent Detours
Keyword(s):  
United States ◽  
Hepatocellular Carcinoma ◽  
Stem Cell ◽  
Risk Groups ◽  
The United States ◽  
Prevention Measures ◽  
Cell Divisions ◽  
Hepatocellular Carcinomas ◽  
Major Subset ◽  
Stem Cell Divisions

Tomasetti and Vogelstein argued that 2/3 of human cancers are due to ‘bad luck’ and that “primary prevention measures [against cancer] are not likely to be very effective”. We demonstrate that their calculations for hepatocellular carcinomas overlooked a major subset of these cancers proven to be preventable through vaccination. The problem, which is not limited to hepatocellular carcinoma, arises from the general reliance of their analysis on average incidences in the United States and the omission of incidences in specific risk groups.

scholarly journals Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in Drosophila male germline stem cell division

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Cuie Chen ◽  
Mayu Inaba ◽  
Zsolt G Venkei ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Mother And Daughter ◽  
Stem Cell Divisions ◽  
Stem Cell Division ◽  
Male Germline Stem Cells

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.

scholarly journals Emerging mechanisms of asymmetric stem cell division

2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Binary Outcomes ◽  
Cellular Mechanisms ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Dividing Cells ◽  
Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

scholarly journals Centrosome-centric view of asymmetric stem cell division

Open Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 200314
Author(s):  
Cuie Chen ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cell ◽  
Recent Progress ◽  
Cell Types ◽  
Cell Fates ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Differential Cell ◽  
Mother And Daughter ◽  
Stem Cell Divisions ◽  
Stem Cell Division

The centrosome is a unique organelle: the semi-conservative nature of its duplication generates an inherent asymmetry between ‘mother’ and ‘daughter’ centrosomes, which differ in their age. This asymmetry has captivated many cell biologists, but its meaning has remained enigmatic. In the last two decades, many stem cell types have been shown to display stereotypical inheritance of either the mother or daughter centrosome. These observations have led to speculation that the mother and daughter centrosomes bear distinct information, contributing to differential cell fates during asymmetric cell divisions. This review summarizes recent progress and discusses how centrosome asymmetry may promote asymmetric fates during stem cell divisions.

scholarly journals Novel insights into mammalian embryonic neural stem cell division: focus on microtubules

2015 ◽  
Vol 26 (24) ◽  
pp. 4302-4306 ◽  
Author(s):  
Felipe Mora-Bermúdez ◽  
Wieland B. Huttner
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Neural Stem Cell ◽  
Spindle Orientation ◽  
Stem Cell Divisions ◽  
A Cell ◽  
Spindle Microtubules ◽  
Stem Cell Division ◽  
Embryonic Neural Stem Cell

During stem cell divisions, mitotic microtubules do more than just segregate the chromosomes. They also determine whether a cell divides virtually symmetrically or asymmetrically by establishing spindle orientation and the plane of cell division. This can be decisive for the fate of the stem cell progeny. Spindle defects have been linked to neurodevelopmental disorders, yet the role of spindle orientation for mammalian neurogenesis has remained controversial. Here we explore recent advances in understanding how the microtubule cytoskeleton influences mammalian neural stem cell division. Our focus is primarily on the role of spindle microtubules in the development of the cerebral cortex. We also highlight unique characteristics in the architecture and dynamics of cortical stem cells that are tightly linked to their mode of division. These features contribute to setting these cells apart as mitotic “rule breakers,” control how asymmetric a division is, and, we argue, are sufficient to determine the fate of the neural stem cell progeny in mammals.

scholarly journals Screens for piwi Suppressors in Drosophila Identify Dosage-Dependent Regulators of Germline Stem Cell Division

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 1971-1991
Author(s):  
Tora K Smulders-Srinivasan ◽  
Haifan Lin
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Genetic Regulation ◽  
Germline Stem Cell ◽  
Transcriptional Level ◽  
Germline Stem Cells ◽  
Somatic Development ◽  
Stem Cell Maintenance ◽  
Stem Cell Divisions ◽  
Stem Cell Division

Abstract The Drosophila piwi gene is the founding member of the only known family of genes whose function in stem cell maintenance is highly conserved in both animal and plant kingdoms. piwi mutants fail to maintain germline stem cells in both male and female gonads. The identification of piwi-interacting genes is essential for understanding how stem cell divisions are regulated by piwi-mediated mechanisms. To search for such genes, we screened the Drosophila third chromosome (∼36% of the euchromatic genome) for suppressor mutations of piwi2 and identified six strong and three weak piwi suppressor genes/sequences. These genes/sequences interact negatively with piwi in a dosage-sensitive manner. Two of the strong suppressors represent known genes—serendipity-δ and similar, both encoding transcription factors. These findings reveal that the genetic regulation of germline stem cell division involves dosage-sensitive mechanisms and that such mechanisms exist at the transcriptional level. In addition, we identified three other types of piwi interactors. The first type consists of deficiencies that dominantly interact with piwi2 to cause male sterility, implying that dosage-sensitive regulation also exists in the male germline. The other two types are deficiencies that cause lethality and female-specific lethality in a piwi2 mutant background, revealing the zygotic function of piwi in somatic development.

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