CD41 (αIIb integrin), a specific marker for megakaryocytes and platelets, was recently shown to mark the initiation of definitive hematopoiesis in mouse embryos. However, whether embryonic CD41+ populations have a nonhematopoietic potential remains elusive. Here, we report that the CD41+ cells from the mouse E11.0 aorta-gonad-mesonephros (AGM) region and yolk sac (YS) expressed a set of mesenchymal markers (as revealed by reverse transcriptase–polymerase chain reaction), displayed myofibroblastic/fibroblastic potential in vitro under mesenchymal culture conditions, and differentiated into α-SMA+/epimorphin+/vimentin+ cells in the lungs of adult recipients after systemic transplantation. This unique cell population with fibroblastic potential expressed intermediate rather than high levels of CD41 and was negative for CD34 in the AGM region. In contrast, circulating CD41+ cells in the embryonic blood stream harbored no similar fibroblastic potential. Compared with the YS, the AGM-derived CD41+ cells had a more robust fibroblastic potential, as revealed by higher in vitro growth rates. Interestingly, the AGM-derived CD41+ cells demonstrated a stronger response to the chemotaxin of circulating blood plasma than the YS-derived CD41+ cells. We are the first group that illustrates the fibroblastic potential of an embryonic CD41+ population in vitro and in vivo, reflecting the close association between blood and mesenchyme development during mouse mid-gestation. The precise origin of these mesenchymal populations needs further clarification.
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References
1.
ChristensenJL, WrightDE, WagersAJ, WeissmanIL. 2004. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol, 2:E75.
2.
MikkolaHK, FujiwaraY, SchlaegerTM, TraverD, OrkinSH. 2003. Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood, 101:508–516.
3.
YaoH, LiuB, WangX, LanY, HouN, YangX, MaoN. 2007. Identification of high proliferative potential precursors with hemangioblastic activity in the mouse aorta-gonad- mesonephros region. Stem Cells, 25:1423–1430.
4.
NorthTE, de BruijnMF, StacyT, TalebianL, LindE, RobinC, BinderM, DzierzakE, SpeckNA. 2002. Runx1 expression marks long-term repopulating HSCs in the midgestation mouse embryo. Immunity, 16:661–672.
5.
BalduiniA, d'ApolitoM, ArcelliD, ContiV, PecciA, PietraD, DanovaM, BenvenutoF, PerottiCet al. 2006. Cord blood in vitro expanded CD41 cells: identification of novel components of megakaryocytopoiesis. J Thromb Haemost, 4:848–860.
6.
Mitjavila-GarciaMT, CailleretM, GodinI, NogueiraMM, Cohen-SolalK, SchiavonV, LecluseY, Le PesteurF, LagrueAH, VainchenkerW. 2002. Expression of CD41 on hematopoietic progenitors derived from embryonic hematopoietic cells. Development, 129:2003–2013.
7.
FerkowiczMJ, StarrM, XieX, LiW, JohnsonSA, ShelleyWC, MorrisonPR, YoderMC. 2003. CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo. Development, 130:4393–4403.
8.
CorbelC, SalaünJ. 2002. AlphaIIb integrin expression during development of the murine hemopoietic system. Dev Biol, 243:301–311.
9.
RobinC, OttersbachK, BoissetJC, OziemlakA, DzierzakE. 2011. CD41 is developmentally regulated and differentially expressed on mouse hematopoietic stem cells. Blood, 117:5088–5091.
10.
Tronik-Le RouxD, RoullotV, PoujolC, KortulewskiT, NurdenP, MarguerieG. 2000. Thrombasthenic mice generated by replacement of the integrin alpha(IIb) gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment. Blood, 96:1399–1308.
11.
BertrandJY, KimAD, TengS, TraverD. 2008. CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis. Development, 135:1853–1862.
12.
YanXL, LanY, WangXY, HeWY, YaoHY, ChenDB, XiongJX, GaoJ, LiZet al. 2011. Migration of dorsal aorta mesenchymal stem cells induced by mouse embryonic circulation. Dev Dyn, 240:65–74.
DuN, FengK, LuoC, LiL, BaiC, PeiX. 2003. Radioprotective effect of FLT3 ligand expression regulated by Egr-1 regulated element on radiation injury of SCID mice. Exp Hematol, 31:191–196.
15.
LiW, FerkowiczMJ, JohnsonSA, ShelleyWC, YoderMC. 2005. Endothelial cells in the early murine yolk sac give rise to CD41-expressing hematopoietic cells. Stem Cells Dev, 14:44–54.
16.
BertrandJY, GirouxS, GolubR, KlaineM, JalilA, BoucontetL, GodinI, CumanoA. 2005. Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. Proc Natl Acad Sci U S A, 102:134–139.
LinG, FingerE, Gutierrez-RamosJC. 1995. Expression of CD34 in endothelial cells, hematopoietic progenitors and nervous cells in fetal and adult mouse tissues. Eur J Immunol, 25:1508–1516.
19.
WoodHB, MayG, HealyL, EnverT, Morriss-KayGM. 1997. CD34 Expression patterns during early mouse development are related to modes of blood vessel formation and reveal additional sites of hematopoiesis. Blood, 90:2300–2311.
20.
HiraiY, TakebeK, TakashinaM, KobayashiS, TakeichiM. 1992. Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell, 69:471–481.
21.
ZhangL, IshikawaO, TakeuchiY, MiyachiY. 1998. Immunohistochemical distribution of epimorphin in human and mouse tissues. Histochem J, 30:903–908.
22.
ZhouJ, ZhaoL, QinL, WangJ, JiaY, YaoH, SangC, HuQ, ShiSet al. 2010. Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. PLoS One, 5:e9732.
23.
JiaY, YaoH, ZhouJ, ChenL, ZengQ, YuanH, ShiL, NanX, WangY, YueW, PeiX. 2011. Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: involvement of small G protein RhoA and C/EBPβJ Cell Physiol, 226:2807–2816.
24.
RadiskyDC, HiraiY, BissellMJ. 2003. Delivering the message: epimorphin and mammary epithelial morphogenesis. Trends Cell Biol, 13:426–434.
25.
NagamotoT, EguchiG, BeebeD. 2000. Alpha-smooth muscle actin expression in cultures lens epithelial cells. Invest Ophthalmol Vis Sci, 41:1122–1129.
26.
FujitaJ, MoriM, KawadaH, IedaY, TsumaM, MatsuzakiY, KawaguchiH, YagiT, YuasaSet al. 2007. Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair. Stem Cells, 25:2750–2759.
27.
DominiciM, PritchardC, GarlitsJE, HofmannTJ, PersonsDA, HorwitzEM. 2004. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. Proc Natl Acad Sci U S A, 101:11761–11766.
28.
WallerEK, OlweusJ, Lund-JohansenF, HuangS, NguyenM, GuoGR, TerstappenL. 1995. The “common stem cell”hypothesis reevaluated: human fetal bone marrow contains separate populations of hematopoietic and stromal progenitors. Blood, 85:2422–2435.
29.
KoideY, MorikawaS, MabuchiY, MugurumaY, HiratsuE, HasegawaK, KobayashiM, AndoK, KinjoK, OkanoH, MatsuzakiY. 2007. Two distinct stem cell lineages in murine bone marrow. Stem Cells, 25:1213–1221.
EbiharaY, MasuyaM, LarueAC, FlemingPA, ViscontiRP, MinamiguchiH, DrakeCJ, OgawaM. 2006. Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes. Exp Hematol, 34:219–229.
32.
LaRueAC, MasuyaM, EbiharaY, FlemingPA, ViscontiRP, MinamiguchiH, OgawaM, DrakeCJ. 2006. Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts associated with solid tumors. Exp Hematol, 34:208–218.
ShiraiK, SeraY, BulkeleyW, MehrotraM, MoussaO, LaRueAC, WatsonDK, StuartRK, LazarchickJ, OgawaM. 2009. Hematopoietic stem cell origin of human fibroblasts: cell culture studies of female recipients of gender-mismatched stem cell transplantation and patients with chronic myelogenous leukemia. Exp Hematol, 37:1464–1471.
35.
TrivediP, HemattiP. 2007. Simultaneous generation of CD34+ primitive hematopoietic cells and CD73+ mesenchymal stem cells from human embryonic stem cells cocultured with murine OP9 stromal cells. Exp Hematol, 35:146–154.
36.
MendesSC, RobinC, DzierzakE. 2005. Mesenchymal progenitor cells localize within hematopoietic sites throughout ontogeny. Development, 132:1127–1136.
37.
KaiserS, HackansonB, FolloM, MehlhornA, GeigerK, IhorstG, KappU. 2007. BM cells giving rise to MSC in culture have a heterogeneous CD34 and CD45 phenotype. Cytotherapy, 9:439–450.
38.
EmambokusNR, FramptonJ. 2003. The glycoprotein IIb molecule is expressed on early murine hematopoietic progenitors and regulates their numbers in sites of hematopoiesis. Immunity, 19:33–45.
39.
BerlangaO, EmambokusN, FramptonJ. 2005. GPIIb (CD41) integrin is expressed on mast cells and influences their adhesion properties. Exp Hematol, 33:403–412.
40.
KumaraveluP, HookL, MorrisonAM, UreJ, ZhaoS, ZuyevS, AnsellJ, MedvinskyA. 2002. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development, 129:4891–4899.
41.
LinHF, TraverD, ZhuH, DooleyK, PawBH, ZonLI, HandinRI. 2005. Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood, 106:3803–3810.
42.
OgawaM, LarueAC, WatsonPM, WatsonDK. 2010. Hematopoietic stem cell origin of mesenchymal cells: opportunity for novel therapeutic approaches. Int J Hematol, 91:353–359.
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