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Chromosome-specific nonrandom sister chromatid segregation during stem-cell division


Adult stem cells undergo asymmetric cell division to self-renew and give rise to differentiated cells that comprise mature tissue1. Sister chromatids may be distinguished and segregated nonrandomly in asymmetrically dividing stem cells2, although the underlying mechanism and the purpose it may serve remain elusive. Here we develop the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique3 with single-chromosome resolution and show that sister chromatids of X and Y chromosomes, but not autosomes, are segregated nonrandomly during asymmetric divisions of Drosophila male germline stem cells. This provides the first direct evidence, to our knowledge, that two sister chromatids containing identical genetic information can be distinguished and segregated nonrandomly during asymmetric stem-cell divisions. We further show that the centrosome, SUN–KASH nuclear envelope proteins and Dnmt2 (also known as Mt2) are required for nonrandom sister chromatid segregation. Our data indicate that the information on X and Y chromosomes that enables nonrandom segregation is primed during gametogenesis in the parents. Moreover, we show that sister chromatid segregation is randomized in germline stem cell overproliferation and dedifferentiated germline stem cells. We propose that nonrandom sister chromatid segregation may serve to transmit distinct information carried on two sister chromatids to the daughters of asymmetrically dividing stem cells.

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Figure 1: Nonrandom segregation of Y and X chromosome strands during GSC divisions.
Figure 2: Autosomes are randomly segregated during GSC divisions.
Figure 3: cnn, koi and klar are required for nonrandom sister chromatid segregation.
Figure 4: Nonrandom segregation of Y and X chromosomes is disrupted in upd-overexpressing testes and dedifferentiated stem cells.


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We thank F. Lyko, M. Schaefer, G. Reuter, P. Zamore, A. Aravin, D. Glover, L. Cooley, J. Kim, V. Gvozdev, M. Pia Bozzetti, the Bloomington Drosophila Stock Center and the Vienna Drosophila RNAi Center for reagents and helpful information, and Yamashita laboratory members for discussions. This study was supported by the University of Michigan (Life Sciences Institute and Office of the Provost and Executive Vice President for Academic Affairs) (to Y.M.Y.) and AHA (12PRE9630000) and NIH grants (1F31HD071727-01) (to S.Y.). Y.M.Y. is supported by the MacArthur Foundation.

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S.Y. conceived the project and developed the single-chromosome CO-FISH protocol for Drosophila cells. S.Y. and Y.M.Y. designed and conducted experiments, interpreted the data, and wrote the manuscript.

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Correspondence to Swathi Yadlapalli or Yukiko M. Yamashita.

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The authors declare no competing financial interests.

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Yadlapalli, S., Yamashita, Y. Chromosome-specific nonrandom sister chromatid segregation during stem-cell division. Nature 498, 251–254 (2013).

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