eli esciences.o g
INSIGHT
HEMATOPOIESIS
New ways o make a blood
cell
In a niche unde he skin in D osophila la ae, blood cells called
plasma ocy es can ans o m in o o he classes o blood cell.
INES ANDERL AND DAN HULTMARK
Rela ed esea ch a icle Lei a
˜o AB, Sucena ´
E.
2015. D osophila sessile hemocy e clus e s a e
ue hema opoie ic issues ha egula e la al
blood cell di e en ia ion. eLi e 4:e06166. doi:
10.7554/eLi e.06166
Image A hemocy e clus e p o ides an
en i onmen ha allows ce ain blood cells
o change in o o he ypes
Abewilde ing a ie y o di e en kinds o
blood cell a e engaged in he immune
de ense o humans, and hey mus all be
p esen in he igh numbe s in he blood.
Unde s anding how blood cells de elop in
humans and o he e eb a es has he e o e
been a ocus o in ense esea ch. A pic u e has
eme ged in which a small numbe o sel -
enewing s em cells gi e ise o mul ipo en
p ogeni o cells, om which successi e gene -
a ions o p ogeni o cells can de elop, each
p og essi ely mo e es ic ed in he ypes o cell
hey can de elop in o. E en ually he p ogeni o
cells gi e ise o he di e en classes o ma u e
blood cells (Doula o e al., 2012;Rie he e al.,
2015). This one-way hie a chical mode o blood
cell o ma ion (o hema opoiesis) akes place in
bone ma ow and o he issues ha p o ide an
en i onmen called a hema opoie ic niche. De-
elopmen al decisions a e con olled by complex
in e ac ions be ween he cells ha make up he
niche and he de eloping blood cells.
Simila p inciples ha e been shown o ope a e
o hema opoiesis in he model o ganism
D osophila melanogas e . A hema opoie ic niche
has been iden i ied in he so-called ‘lymph
glands’ o D osophila la ae, which a e ound in
an a ea called he pos e io signaling cen e. This
niche con ols he p oli e a ion and specializa-
ion—o ‘di e en ia ion’—o adjacen s em cells
and/o p ogeni o cells (K zemie ´
n e al., 2007;
Mandal e al., 2007). Now, in eLi e, Alexand e
Lei a
˜o and ´
Elio Sucena o he Ins i u o Gulben-
kian de Ci ˆ
encia in Po ugal challenge he no ion
ha hema opoiesis occu s h ough a nea ansi-
ion om s em cells ia p ogeni o cells o
di e en ia ed blood cells. Ins ead, hey show
ha some di e en ia ed blood cells can ans-
o m in o blood cells o ano he class (Lei a
˜o and
Sucena, 2015).
Th ee majo classes o blood cells, o hemo-
cy es, can be dis inguished in D osophila:
plasma ocy es, c ys al cells and lamellocy es
(Figu e 1). Mos abundan a e he plasma o-
cy es. These a e p o essional phagocy es—cells
ha engul and des oy bac e ia and cells ha
a e p og ammed o die. C ys al cells a e in ol ed
in wound healing and con ol he p oduc ion o
he black pigmen melanin. Finally, lamellocy es
a e specialized o espond o pa asi e in ec ion,
which hey do by o ming a capsule a ound he
pa asi e.
D osophila hemocy es a e gene a ed in wo
dis inc wa es du ing de elopmen (Holz e al.,
2003). The i s gene a ion o hemocy es o ms in
issue in he head o he emb yo and pe sis s in
he ly un il adul hood. Emb yonic plasma ocy es
om his i s gene a ion colonize he su aces o
la al issues, o ming sessile clus e s o hemo-
cy es ha cons an ly exchange cells wi h hei
ci cula ing coun e pa s. Con enien ly, many o
Copy igh Ande l and Hul ma k.
This a icle is dis ibu ed unde he
e ms o he C ea i e Commons
A ibu ion License, which pe mi s
un es ic ed use and edis ibu ion
p o ided ha he o iginal au ho and
sou ce a e c edi ed.
Ande l and Hul ma k. eLi e 2015;4:e06877. DOI: 10.7554/eLi e.06877 1o 3
hese clus e s a e loca ed in pa ches unde he
skin, so esea che s can obse e hem di ec ly
(Figu e 1A). The plasma ocy es di ide and he
o al numbe o hemocy es inc eases g adually
du ing la al de elopmen . As shown by Ka ja
B ¨
uckne and co-wo ke s in 2011, plasma ocy es
p oli e a e mos ac i ely in he sessile subepi he-
lial pa ches, whe e cell di ision appea s o be
con olled by he pe iphe al ne ous sys em
(Makhijani e al., 2011).
A second gene a ion o hemocy es o ms in
he lymph glands. Unde no mal condi ions,
he lymph glands do no elease hemocy es
un il me amo phosis, a he end o he la al
s age. Up o ha poin all ci cula ing la al
hemocy es belong o he i s gene a ion o
blood cells.
In 1957, Tahi Rizki p oposed a model in which
pa asi e in ec ion causes plasma ocy es o ans-
o m in o lamellocy es; he model also assumes
ha plasma ocy es and c ys al cells independen ly
o igina e om p ogeni o cells dubbed p ohemo-
cy es (Rizki, 1957). Howe e , wo k on hema o-
poiesis in he lymph glands sugges ed a di e en
model, whe e all h ee hemocy e classes o igina e
di ec ly om undi e en ia ed p ecu so cells
(E ans e al., 2003). Fu he mo e, he lymph
glands espond igo ously o pa asi e in ec ion,
p oducing lamellocy es and o he hemocy es
ha a e p ema u ely eleased in o ci cula ion
(Figu e 1B). I was he e o e gene ally assumed
ha helymphglandsa e hemajo sou ceo
cells o he immune de ense. Howe e , ans-
plan a ion and lineage acing s udies ha e ecen ly
shown ha mos lamellocy es s em di ec ly om
i s gene a ion la al plasma ocy es (M´
a kus e al.,
2009;Hon i e al., 2010;S o anko e al., 2010), in
line wi h Rizki’s o iginal p oposal.
Lei a
˜o and Sucena ha e now ca e ully s udied
c ys al cell de elopmen in he subepi helial
pa ches. An obs acle o simila s udies in he
pas has been ha la ae a e e y mo ile, and
Figu e 1. Fluo escen ma ke genes e eal he di e en blood cell ypes in heal hy and in ec ed D osophila la ae.
(A) Blood cells in a heal hy la a: plasma ocy es a e in g een and c ys al cells a e in magen a; whi e indica es he
p esence o bo h ypes o cell. Sessile blood cells o he i s gene a ion o m a pa e n o pa ches unde he skin.
Second gene a ion blood cells accumula e in he ‘lymph glands’ (which a e no ela ed o e eb a e lymph glands in
s uc u e o unc ion). Ci cula ing blood cells do no gi e sha p images. (B) La ge numbe s o lamellocy es ( ed)
accumula e in la ae in ec ed by pa asi oid wasp eggs, a aching o he eggs and o he pa s o he la a. The sessile
blood cells become dispe sed, he p ima y lobes o he lymph glands elease hei con en s, and he seconda y
lobes enla ge.
Ande l and Hul ma k. eLi e 2015;4:e06877. DOI: 10.7554/eLi e.06877 2o 3
Insigh Hema opoiesis | New ways o make a blood cell
hei busy pe is al ic mo emen s make i di icul
o ace he a e o indi idual cells. Lei a
˜o and
Sucena sol ed his p oblem by using double-
sided ape o hold he la ae s ill. By inse ing
luo escen genes in o he la ae ha p oduce
di e en colo s in di e en cell ypes, he de-
elopmen al a e o indi idual hemocy es could
hen be ollowed o up o h ee hou s using
ime-lapse imaging. Unexpec edly, Lei a
˜o and
Sucena disco e ed ha plasma ocy es occasion-
ally ans o m in o c ys al cells, a a a e consis-
en wi h he inc ease in he o e all numbe o
c ys al cells in he la a. Thus, s ikingly, hema o-
poiesis occu s in he subepi helial pa ches o
D osophila la ae wi hou he in ol emen o
s em cells.
A hema opoie ic niche is ne e heless e-
qui ed, e en in his no el mode o hema opoie-
sis. Lei a
˜o and Sucena show ha he decision o
begin de eloping a plasma ocy e in o a c ys al
cell is igge ed by signals om neighbo ing
plasma ocy es in he subepi helial pa ches ia he
No ch signalling pa hway. In a pleasing ag ee-
men wi h his model, he p obabili y ha a cell
becomes a c ys al cell is p opo ional o he
numbe o plasma ocy es i is in con ac wi h.
Fu he mo e, c ys al cell o ma ion is inhibi ed
when hemocy es a e physically p e en ed om
se ling.
Hence, wo dis inc ypes o hema opoiesis
coexis in D osophila la ae; one in he lymph
glands, whe e a niche con ols he di e en ia ion
o s em cells, and ano he unde he skin, whe e
a niche con ols how al eady di e en ia ed
plasma ocy es ans o m in o c ys al cells and,
when needed, lamellocy es.
Ines Ande l is in he Labo a o y o Gene ic Immunol-
ogy, BioMediTech, Uni e si y o Tampe e, Tampe e,
Finland and he Depa men o Molecula Biology,
Ume˚
a Uni e si y, Ume˚
a, Sweden
Dan Hul ma k is in he Depa men o Molecula
Biology, Ume˚
a Uni e si y, Ume˚
a, Sweden and he
Labo a o y o Gene ic Immunology, BioMediTech,
Uni e si y o Tampe e, Tampe e, Finland
[email p o ec ed]
Compe ing in e es s: The au ho s decla e ha no
compe ing in e es s exis .
Published 12 Ma ch 2015
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˜oAB, Sucena ´
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egula e la al blood cell di e en ia ion. eLi e 4:
e06166. doi: 10.7554/eLi e.06166.
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Ande l and Hul ma k. eLi e 2015;4:e06877. DOI: 10.7554/eLi e.06877 3o 3
Insigh Hema opoiesis | New ways o make a blood cell