10. T. Kiørboe, G. Jackson, Limnol. Oceanogr. 46, 1309
11. J. Muñoz-García, Z. Neufeld, C. Torney, New J. Phys. 12,
12. P. Moin, K. Mahesh, Annu. Rev. Fluid Mech. 30, 539
13. D. Donzis, K. Sreenivasan, P. Yeung, Flow Turbul. Combus.
85, 549 (2010).
14. G. Batchelor, J. Fluid Mech. 5, 113 (1959).
15. T. Ahmed, R. Stocker, Biophys. J. 95, 4481 (2008).
16. Supplementary materials are available on Science
17. P. Williams, in Microbial Ecology of the Oceans,
D. L. Kirchman, Ed. (Wiley, New York, 2000),
18. L. Xie, T. Altindal, S. Chattopadhyay, X. L. Wu, Proc. Natl.
Acad. Sci. U.S.A. 108, 2246 (2011).
19. A. Hütz, K. Schubert, J. Overmann, Appl. Environ. Microbiol.
77, 4412 (2011).
20. M. Gregg, D. Winkel, T. Sanford, H. Peters, Dyn. Atmos.
Oceans 24, 1 (1996).
21. E. F. DeLong et al., Science 311, 496 (2006).
22. D. Grünbaum, Hydrobiologia 480, 175 (2002).
23. R. M. Morris et al., Nature 420, 806 (2002).
24. E. Purcell, Am. J. Phys. 45, 3 (1977).
25. H. Grossart, L. Riemann, F. Azam, Aquat. Microb. Ecol.
25, 247 (2001).
26. C. Matz, K. Jürgens, Appl. Environ. Microbiol. 71, 921
27. J. Seymour, Marcos, R. Stocker, Am. Nat. 173, E15 (2009).
28. J. Crimaldi, H. Browning, J. Mar. Syst. 49, 3 (2004).
29. W. M. Durham, E. Climent, R. Stocker, Phys. Rev. Lett.
106, 238102 (2011).
30. J. Marshall, Y. Huang, Chem. Eng. Sci. 65, 3865
Acknowledgments: We thank W. M. Durham, R. Ferrari,
M. Follows, M. Garren, F. Menolascina, S. Merrifield,
T. Pedley, S. Smriga, and R. Watteaux for helpful
comments and suggestions. The calculation of the
resistive force coefficient for a bacterium was performed
by Marcos. J.R. T. was supported by an NSF Mathematical
Sciences Postdoctoral Research Fellowship. R.S. acknowledges
NSF grants OCE-0744641-CAREER and CBET-1066566.
20 January 2012; accepted 2 August 2012
Materials and Methods
Figs. S1 to S9
Asymmetric Division of Drosophila
Male Germline Stem Cell Shows
Asymmetric Histone Distribution
Vuong Tran,* Cindy Lim,* Jing Xie, Xin Chen†
Stem cells can self-renew and generate differentiating daughter cells. It is not known whether
these cells maintain their epigenetic information during asymmetric division. Using a dual-color
method to differentially label “old” versus “new” histones in Drosophila male germline stem
cells (GSCs), we show that preexisting canonical H3, but not variant H3.3, histones are selectively
segregated to the GSC, whereas newly synthesized histones incorporated during DNA replication
are enriched in the differentiating daughter cell. The asymmetric histone distribution occurs
in GSCs but not in symmetrically dividing progenitor cells. Furthermore, if GSCs are genetically
manipulated to divide symmetrically, this asymmetric mode is lost. This work suggests that
stem cells retain preexisting canonical histones during asymmetric cell divisions, probably as a
mechanism to maintain their unique molecular properties.
Although all cells in an organism con- tain the same genetic material, differ- ent genes are expressed in specific cell
types, allowing them to differentiate along distinct pathways. Epigenetic mechanisms regulate
gene expression and maintain a specific cell
fate through many cell divisions (1–3). Stem cells
have the remarkable ability to both self-renew and
generate daughter cells that enter differentiation
(4). Epigenetic mechanisms have been reported
to regulate stem cell activity in multiple lineages
(5–7). However, there has been little direct in
vivo evidence demonstrating whether stem cells
retain their epigenetic information.
The Drosophila male GSCs are well characterized in terms of their physiological location, microenvironment (i.e., niche), and
cellular structures (8, 9) (Fig. 1, A and B).
Male GSCs can be identified precisely by their
distinct anatomical positions and morpholog-
Department of Biology, Johns Hopkins University, Baltimore,
MD 21218, USA.
*These authors contributed equally to this work.
†To whom correspondence should be addressed. E-mail:
ical features. A GSC usually divides asymmetrically to produce a self-renewed GSC and
a daughter cell gonialblast (GB) that undergoes differentiation. Therefore, GSCs can be
examined at single-cell resolution for a direct
In eukaryotes, the basic unit of chromatin
called nucleosome contains histone octamer
[2×(H3, H4, H2A, H2B)] and DNA wrapping
around them. Indeed, histones are one of the
major carriers of epigenetic information (10).
To address how histones are distributed during
the GSC asymmetric division, we developed a
switchable dual-color method to differentially
label “old” versus “new” histones (Fig. 1C) that
uses both spatial (by Gal4; UAS system) and
temporal (by heat shock induction) controls to
switch labeled histones from green [green fluores-
cent protein (GFP)] to red [monomeric Kusabira-
Orange (mKO)]. Heat shock treatment induces
an irreversible DNA recombination to shut down
expression of GFP-labeled old histones and ini-
tiate expression of mKO-labeled new histones.
If the old histones are partitioned nonselective-
ly, the GFP will initially exhibit equal distribu-
tion in the GSC and GB, and will be gradually
replaced by the mKO (Fig. 1D). However, if
the old histones are preferentially retained in
the GSCs to constitute potentially GSC-specific
chromatin structure, the GFP will be detected
specifically in the GSCs (Fig. 1E). During DNA
replication–dependent canonical histone depo-
sition, histones H3 and H4 are incorporated as a
tetramer, and histones H2A and H2B are incorpo-
rated as dimers (11–15). Therefore, we generated
independent transgenic strains for H3 and H2B,
respectively. On the other hand, histone variants
are incorporated into chromatin in a transcription-
coupled but DNA replication–independent man-
ner (16, 17). Therefore, the histone variant H3.3
was used as a control for canonical histones.