Aneuploidy Causes Premature Differentiation of Neural and Intestinal Stem Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Nov 18

PMID 26573328

Citations 41

Authors

Delphine Gogendeau

Katarzyna Siudeja

Davide Gambarotto

Carole Pennetier

Allison J Bardin

Renata Basto

Affiliations

Soon will be listed here.

Abstract

Aneuploidy is associated with a variety of diseases such as cancer and microcephaly. Although many studies have addressed the consequences of a non-euploid genome in cells, little is known about their overall consequences in tissue and organism development. Here we use two different mutant conditions to address the consequences of aneuploidy during tissue development and homeostasis in Drosophila. We show that aneuploidy causes brain size reduction due to a decrease in the number of proliferative neural stem cells (NSCs), but not through apoptosis. Instead, aneuploid NSCs present an extended G1 phase, which leads to cell cycle exit and premature differentiation. Moreover, we show that this response to aneuploidy is also present in adult intestinal stem cells but not in the wing disc. Our work highlights a neural and intestine stem cell-specific response to aneuploidy, which prevents their proliferation and expansion.

Citing Articles

The RNA-binding protein Modulo promotes neural stem cell maintenance in Drosophila.

Parra A, Johnston C PLoS One. 2024; 19(12):e0309221.

PMID: 39700092 PMC: 11658480. DOI: 10.1371/journal.pone.0309221.

Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex.

Naher S, Iemura K, Miyashita S, Hoshino M, Tanaka K, Niwa S EMBO J. 2024; 44(2):331-355.

PMID: 39632980 PMC: 11729872. DOI: 10.1038/s44318-024-00327-7.

Arsenic impairs neural stem cell mitotic progression and sleep behavior in a tauopathy model.

Adebambo T, Flores M, Zhang S, Lerit D bioRxiv. 2024; .

PMID: 39149321 PMC: 11326188. DOI: 10.1101/2024.08.05.606375.

Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids.

Johnson B, Liu A, Bi T, Dong Y, Li T, Zhou D Mol Biol Cell. 2024; 35(8):br15.

PMID: 38985518 PMC: 11321050. DOI: 10.1091/mbc.E24-04-0166.

Genome-Wide Expression Analysis of Long Noncoding RNAs and Their Target Genes in Metafemale .

Liu X, Yan R, Liu H, Zhang S, Wang R, Zhang B Int J Mol Sci. 2023; 24(9).

PMID: 37176087 PMC: 10179461. DOI: 10.3390/ijms24098381.

References

Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe S . Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell. 2006; 11(1):9-23. PMC: 1850996. DOI: 10.1016/j.ccr.2006.10.019. View

Caussinus E, Gonzalez C . Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet. 2005; 37(10):1125-9. DOI: 10.1038/ng1632. View

Siegel J, Amon A . New insights into the troubles of aneuploidy. Annu Rev Cell Dev Biol. 2012; 28:189-214. PMC: 3919630. DOI: 10.1146/annurev-cellbio-101011-155807. View

Brand A, Perrimon N . Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993; 118(2):401-15. DOI: 10.1242/dev.118.2.401. View

Lara-Gonzalez P, Westhorpe F, Taylor S . The spindle assembly checkpoint. Curr Biol. 2012; 22(22):R966-80. DOI: 10.1016/j.cub.2012.10.006. View

Rahmani Z, Gagou M, Lefebvre C, Emre D, Karess R . Separating the spindle, checkpoint, and timer functions of BubR1. J Cell Biol. 2009; 187(5):597-605. PMC: 2806589. DOI: 10.1083/jcb.200905026. View

Calegari F, Haubensak W, Haffner C, Huttner W . Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development. J Neurosci. 2005; 25(28):6533-8. PMC: 6725437. DOI: 10.1523/JNEUROSCI.0778-05.2005. View

Silkworth W, Nardi I, Scholl L, Cimini D . Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS One. 2009; 4(8):e6564. PMC: 2719800. DOI: 10.1371/journal.pone.0006564. View

Crasta K, Ganem N, Dagher R, Lantermann A, Ivanova E, Pan Y . DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012; 482(7383):53-8. PMC: 3271137. DOI: 10.1038/nature10802. View

10.

Arai Y, Pulvers J, Haffner C, Schilling B, Nusslein I, Calegari F . Neural stem and progenitor cells shorten S-phase on commitment to neuron production. Nat Commun. 2011; 2:154. PMC: 3105305. DOI: 10.1038/ncomms1155. View

11.

Hammerle B, Ulin E, Guimera J, Becker W, Guillemot F, Tejedor F . Transient expression of Mnb/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling. Development. 2011; 138(12):2543-54. PMC: 3100710. DOI: 10.1242/dev.066167. View

12.

Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A . Centrosome amplification can initiate tumorigenesis in flies. Cell. 2008; 133(6):1032-42. PMC: 2653712. DOI: 10.1016/j.cell.2008.05.039. View

13.

Weissbein U, Benvenisty N, Ben-David U . Quality control: Genome maintenance in pluripotent stem cells. J Cell Biol. 2014; 204(2):153-63. PMC: 3897183. DOI: 10.1083/jcb.201310135. View

14.

Brodsky M, Nordstrom W, Tsang G, Kwan E, Rubin G, Abrams J . Drosophila p53 binds a damage response element at the reaper locus. Cell. 2000; 101(1):103-13. DOI: 10.1016/S0092-8674(00)80627-3. View

15.

Uetake Y, Sluder G . Prolonged prometaphase blocks daughter cell proliferation despite normal completion of mitosis. Curr Biol. 2010; 20(18):1666-71. PMC: 2946429. DOI: 10.1016/j.cub.2010.08.018. View

16.

Lai S, Miller M, Robinson K, Doe C . The Snail family member Worniu is continuously required in neuroblasts to prevent Elav-induced premature differentiation. Dev Cell. 2012; 23(4):849-57. PMC: 3509944. DOI: 10.1016/j.devcel.2012.09.007. View

17.

Becker K, Ghule P, Therrien J, Lian J, Stein J, van Wijnen A . Self-renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase. J Cell Physiol. 2006; 209(3):883-93. DOI: 10.1002/jcp.20776. View

18.

Sousa-Nunes R, Cheng L, Gould A . Regulating neural proliferation in the Drosophila CNS. Curr Opin Neurobiol. 2010; 20(1):50-7. DOI: 10.1016/j.conb.2009.12.005. View

19.

Coronado D, Godet M, Bourillot P, Tapponnier Y, Bernat A, Petit M . A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency. Stem Cell Res. 2012; 10(1):118-31. DOI: 10.1016/j.scr.2012.10.004. View

20.

Rujano M, Sanchez-Pulido L, Pennetier C, Le Dez G, Basto R . The microcephaly protein Asp regulates neuroepithelium morphogenesis by controlling the spatial distribution of myosin II. Nat Cell Biol. 2013; 15(11):1294-306. DOI: 10.1038/ncb2858. View