New ways to make a blood cell

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 Re e ences Doula o S, No a F, Lau en i E, Dick JE. 2012. Hema opoiesis: a human pe spec i e. 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