genes from both signatures. Thus, scRNA-seq
analysis reveals the alternative expression of the
stem/memory and effector signatures in the two
cell types, respectively, and the concomitant low
or high expression of these two signatures in the
cycling cells. These results suggest that cycling
cells may represent bipotent differentiation intermediates expressing both effector and stem/memory
potential. Furthermore, the commitment to effector
differentiation paths appears to be acquired by
the silencing of stem/memory genes.
The total number of unique molecular identifiers (UMI) measured in each subset category did
not differ between wild-type and Suv39h1-KO cells
(fig. S17, A and B). Naïve, cycling, and memory
Suv39h1-KO cells bear similar patterns of gene
expression signatures as compared to wild-type cells.
In contrast, a significant difference was observed
in effector cells, in which the numbers of stem/
memory genes per cell were increased relative to
effector cells from wild-type mice. The proportion
of cells expressing more than 10 genes from the
stem/memory signature was augmented from
16% in the wild type to 34% in effector Suv39h1-KO
cells. Thus, rather than a specific subpopulation of
stem/memory cells accumulating in the Suv39h1-
KO mice, the expression of stem/memory-related
genes was derepressed mainly in Suv39h1-KO
effector T cells.
We argue that after priming, cycling CD8+ T
lymphocytes reprogram both self-renewing and
effector gene expression profiles (Fig. 6I). These
cycling cells may represent bipotent intermediates, which would then repress either the effector
or stem cell/memory programs while they differentiate to memory precursors or effectors, respectively (Fig. 6I). The silencing of the stem
cell/memory gene expression program is under
the control of Suv39h1 by imposing the H3K9me3
modification on chromatin at the corresponding
loci. In doing so, Suv39h1/H3K9me3 would establish an epigenetic barrier on the stem/memory
gene expression program, preventing effector reprograming into memory cells (Fig. 6I). It is
most likely that the possibly reversible silencing of effector gene expression in memory cells
occurs through other mechanisms, as memory
cells do effectively reprogram into effectors upon
rechallenge. These results open new perspectives
for the manipulation of epigenetic programming
of T lymphocyte identity in the context of vaccination, checkpoint-based immunotherapies, and
adoptive T cell therapies.
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We thank all the U932 and UMR3664 members; C. Maison,
N. Lacoste, and F. X. Gobert for helpful discussions; A. Cros and
V. Mondin for technical help; B. Amati and J. Sedat for critical reading of
the manuscript; the flow cytometry platform, the genomic and animal
facilities, the Nikon Imaging Center of Curie Institute; and the PIC T-IBISA@PasteurImagingfacility.WethankT.Je nuwein for providing the
SUV39H1 gene and the Suv39h1-KO mice. LM-OVA was kindly provided
by H. Shen. Supported by the Institute Curie, Institut National de la
Santé et de la Recherche Médicale, Centre National de la Recherche
Scientifique, ANR “Chroma Tin” grant ANR-10-BLAN-1326-03, and
“EPICURE” grant ANR-14-CE16-0009 (S. A. and G. A.); la Ligue Contre le
Cancer (Equipe labelisée Ligue, EL2014.LNCC/SA) and Association de
Recherche Contre le Cancer grant ERC (2013-Ad G N° 340046 DCBIOX)
(S.A.); la Ligue Nationale contre le Cancer (Equipe labelisée Ligue), the
European Commission Network of Excellence EpiGeneSys (HEALTH-
F4-2010-257082), ERC Advanced Grant 2009-AdG_20090506
“Eccentric,” the European Commission large-scale integrating project
FP7_HEALTH-2010-259743 “MODHEP,” ANR-11-LABX-0044_DEEP,
ANR-10-IDEX-0001-02 PSL, ANR “CHAPINHIB” ANR-12-BSV5-0022-
02, ANR “CELLECTCHIP” ANR-14-CE10-0013, and the Aviesan-ITMO
cancer project “Epigenomics of breast cancer” (G. A.); and SiRIC/INCa
grant INCa-DGOS-4654 (J.J. W.). High-throughput sequencing was
performed by the ICGex NGS platform of the Institut Curie supported
by the grants SESAME (région Ile-de-France), ANR-10-EQPX-03, and
ANR-10-INBS-09-08. The bioinformatics data are available in the Gene
Expression Omnibus (GEO) database under accession numbers
GSE105163 (microarrays) and SuperSeries GSE106268 for ChIP-seq and
scRNA-seq data (linked to subseries GSE106264, GSE106265, and
GSE106267). The authors have no conflicting financial interests. The data
are tabulated in the main paper and in the supplementary materials. Author
contributions: L.P. conceived and designed the project, carried out
experimental work, and wrote the manuscript; C.G. contributed to
bioinformatics design, carried out bioinformatics work, and interpreted
data; E.Z. contributed to project design, carried out experimental work,
and interpreted data; P. G. carried out bioinformatics work and
participated in data interpretation; N.B. carried out experimental work;
J. J. W. participated in bioinformatics data analysis and interpretation;
J.-P.Q. participated in project design and data interpretation and wrote
the manuscript; G.A. designed the project and wrote the manuscript;
and S.A. conceived and designed the project and wrote the manuscript.
L.P., C.G., and S. A. are inventors on patent application EP17305757.1
submitted by Institut Curie that covers the targeting of Suv39h1 in the
context of T cell adoptive transfer.
Materials and Methods
Figs. S1 to S17
Tables S1 to S5
27 July 2016; resubmitted 1 August 2017
Accepted 16 November 2017
Coherent band excitations in CePd3:
A comparison of neutron scattering
and ab initio theory
Eugene A. Goremychkin,1 Hyowon Park,2,3 Raymond Osborn,2 Stephan Rosenkranz,2
John-Paul Castellan,2,4 Victor R. Fanelli,5 Andrew D. Christianson,6 Matthew B. Stone,6
Eric D. Bauer,7 Kenneth J. McClellan,7 Darrin D. Byler,7 Jon M. Lawrence7,8
In common with many strongly correlated electron systems, intermediate valence compounds
are believed to display a crossover from a high-temperature regime of incoherently fluctuating
local moments to a low-temperature regime of coherent hybridized bands. We show that
inelastic neutron scattering measurements of the dynamic magnetic susceptibility of CePd3
provides a benchmark for ab initio calculations based on dynamical mean field theory. The
magnetic response is strongly momentum dependent thanks to the formation of coherent
f-electron bands at low temperature, with an amplitude that is strongly enhanced by local
particle-hole interactions. The agreement between experiment and theory shows that we have a
robust first-principles understanding of the temperature dependence of f-electron coherence.
The Anderson impurity model, used to de- scribe magnetic impurities in metals, formu- lates the interaction of localized f-electron orbitals with more delocalized d-electron bands through an onsite hybridization, whose
strength is typically represented by a single energy
scale, the Kondo temperature, TK (1). It has been
successfully applied to intermediate valence com-
pounds, such as CePd3 and CeSn3, even though
the f electrons in these materials are not on iso-
lated impurities but sit on a periodic lattice (2).
Nevertheless, various deviations from the expected
186 12 JANUARY 2018 • VOL 359 ISSUE 6372 sciencemag.org SCIENCE
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