Science - 6 December 2019

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^

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