Science - 06.12.2019

(singke) #1
SCIENCE sciencemag.org

STEM CELLS

Lymphatic vessels


as a stem cell niche


Reciprocal signaling between lymphatic vessels


and hair follicle stem cells drives skin regeneration


ByNatasha L. Harvey

L

ymphatic vessels play crucial roles in
tissue fluid homeostasis, immune cell
trafficking, and dietary lipid absorp-
tion. An extensive network of lym-
phatic vessels beneath the epidermis
provide a highway for the transport of
immune cells that patrol the skin to lymph
nodes, where antigens are presented to the
immune system for surveillance ( 1 ). On
page 1218 of this issue, Gur-Cohen et al. ( 2 )
reveal that in addition to regulating inter-
stitial fluid balance and directing immune
cell traffic, lymphatic vessels in mouse skin
comprise an important stem cell niche.
This intriguing work demonstrates that
superficial lymphatic vessels located in
the dermis share an intimate and dynamic
spatial association with hair follicle stem
cells (HFSCs) and that signaling between
these two compartments coordinates hair
follicle cycling and skin regeneration.
Stem cell niches are specialized microen-
vironments within tissue, often comprising
multiple cell types, that support stem cell
activity. Extensive evidence demonstrates
that blood vessels are an integral compo-

nent of stem cell niches in tissues, includ-
ing in bone marrow, muscle, and brain ( 3 ).
However, the role of lymphatic vessels in
regulating stem cell activity has, until now,
remained unexplored. Gur-Cohen et al.
used recent advances in imaging technol-
ogy to reveal that superficial, initial lym-
phatic vessels, which form a stereotypical
pattern throughout skin, envelope hair fol-
licles and share particularly close contact
with HFSCs. Initial lymphatic vessels are
specialized for fluid absorption. Their char-
acteristics include prominent expression
of lymphatic vessel endothelial hyaluronan
acid receptor 1 (LYVE1) on lymphatic endo-
thelial cells, which line the vessel ( 4 ), and
relatively loose, button-like endothelial cell
junctions that enable the entry of fluid and
cellular traffic to this part of the lymphatic
vasculature ( 5 ). Fluid, macromolecules,
and immune cells taken up by the initial
lymphatics are drained into precollecting
and collecting lymphatic vessels, which
exhibit a distinct identity and are special-
ized to return lymph to the bloodstream.
Collecting vessels have tighter, zipper-like
endothelial cell junctions, contain valves,
and are surrounded by vascular smooth

Growth
Increased ANGPTL4, reduced lymphatic drainage

Quiescence
Increased ANGPTL7

Valve

Hair

Smooth muscle cells

HFSCS

Initial vessel Progenitor cells Collecting
vessel

GRAPHIC: V. ALTOUNIAN/


SCIENCE


time scales of the 4.3-hour rotation period.
Both the meteorite flux and the temperature
at 2 cm depth should peak in the local after-
noon, which lines up with the timing of the
major particle ejections.
The discovery of particle ejections is sur-
prising and may suggest that all asteroids
are active at some level. However, previous
spacecraft that have visited asteroids have
not documented this type of event. Key an-
swers may come from the Hayabusa2 mission
by the Japan Aerospace Exploration Agency
to the asteroid Ryugu ( 10 ), which resembles
Bennu in terms of shape, density and orbit
but likely is composed of different material.
Like OSIRIS-REx, Hayabusa2 is character-
izing the asteroid in great detail in order to
bring back a sample of it in 2020. The pres-
ence or absence of activity will provide some
additional constraints on the low-level activ-
ity of small asteroids.
The Bennu observations leave open a ques-
tion of how to predict such low-level activ-
ity of the many millions of asteroids not tar-
geted for missions. Estimating the amount
of debris that is released into interplanetary
space is clearly important but very challeng-
ing. Depending on the driving process for
Bennu’s ejections, there may or may not be a
continuum between it and “classically” active
asteroids. The activity on Bennu shows that
an apparently inactive asteroid can harbor a
complex dynamic of debris reimpacting the
surface or feeding the interplanetary dust
cloud. This process may have implications for
Bennu’s evolution. A similar observation was
made at comet 67P/Churyumov-Gerasimenko
by the European Space Agency’s Rosetta mis-
sion, which found small outbursts of gas
and debris emission through the comet’s
entire perihelion passage ( 11 ). Earth-based
telescopes did not pick up this activity ( 12 ).
Isolating the detailed processes across differ-
ent scales that drive activity on asteroids and
comets is important to understand the evolu-
tion of these bodies and how they supply dust
to interplanetary space. j
REFERENCES AND NOTES


  1. D. S. Lauretta et al., Science 366 , eaay3544 (2019).

  2. E. W. Elst et al., IAU Circular 6456 (1996).

  3. H. H. Hsieh, D. C. Jewitt, Y. R. Fernández, Astron. J. 127 ,
    2997 (2004).

  4. H. H. Hsieh, D. Jewitt, Science 312 , 561 (2006).

  5. M. Ishiguro et al., Astrophys. J. 741 , L24 (2011).

  6. D. Jewitt et al., in Asteroids IV, P. Michel et al., eds. (Univ.
    Arizona Press, 2015).

  7. D. S. Lauretta et al., Nature 568 , 55 (2019).

  8. D. N. DellaGiustina et al., New Astron. 3 , 341351 (2019).

  9. D. S. Lauretta et al., Space Sci. Rev. 212 , 925 (2017).

  10. S. Watanabe et al., Science 364 , 268 (2019).

  11. J.-B. Vincent et al., Mon. Not. R. Astron. Soc. 462
    (suppl.1), S184 (2016).

  12. H. Böhnhardt et al., Mon. Not. R. Astron. Soc. 462 , S376
    (2016).
    ACKNOWLEDGMENTS
    This work was supported by the European Research Council
    Starting Grant 757390 “CAstRA.”
    10.1126/science.aaz7129


INSIGHTS

The hair follicle stem cell niche
During quiescence, hair follicle stem cells (HFSCs) produce factors, including angiopoietin-related protein 7
(ANGPTL7), that maintain contact between HFSCs and initial lymphatic vessels and promote lymphatic
vessel drainage. The shift of HFSCs to the production of ANGPTL4 results in dissociation of lymphatic vessels
from the HFSC niche, reduced lymphatic drainage, and hair growth.

6 DECEMBER 2019 • VOL 366 ISSUE 6470 1193
Published by AAAS

on December 12, 2019^

http://science.sciencemag.org/

Downloaded from
Free download pdf