et al., Eur. J. Neurosci. 11, 567 (1999); E. E. Smith, J.Jonides, R. A. Koeppe, Cereb. Cortex 6, 11 (1996)].However, activation has been consistently reportedin this area when participants are asked to monitor ormanipulate items in memory in tasks such as theself-ordered task [M. Petrides, B. Alivisatos, E. Meyer,A. C. Evans, Proc. Natl. Acad. Sci. U.S.A. 90, 873(1993)] or search task [A. M. Owen, A. C. Evans, M.Petrides, Cereb. Cortex 6, 31 (1996)].

6. In n-back tasks, participants are required to monitora series of spatial items [E. E. Smith, J. Jonides, R. A.Koeppe, Cereb. Cortex 6, 11 (1996); M. D’Esposito etal., Neuroimage 8, 274 (1998); A. M. Owen et al.,Proc. Natl. Acad. Sci. U.S.A. 95, 7721 (1998)] orverbal items [M. D’Esposito, D. Ballard, G. K. Aguirre,E. Zarahn, Neuroimage 8, 274 (1998); J. D. Cohen etal., Hum. Brain Mapp. 1, 293 (1994); J. D. Cohen etal., Nature 386, 604 (1997); D. M. Barch et al.,Neuropsychologia 35,1373 (1997); M. D’Esposito,B. R. Postle, D. Ballard, J. Lease, Brain Cognition 41, 66(1999)] and report when an item is repeated after “n”trials.

7. M. Petrides, in Handbook of Neuropsychology, F.Boller and J. Grafman, Eds. (Elsevier, Amsterdam,1994), vol. 9, pp. 59–82.

8. C. D. Frith, K. Friston, P. F. Liddle, R. S. Frackowiak,Proc. R. Soc. London Ser. B. 244, 241 (1991); M.Jueptner et al., J. Neurophysiol. 77, 1313 (1997); M.Jueptner, C. D. Frith, D. J. Brooks, R. S. J. Frackowiak,R. E. Passingham, J. Neurophysiol. 77, 1325 (1997);J. E. Desmond, J. D. E. Gabrieli, G. H. Glover, Neuro-image 7, 368 (1998); S. A. Spence, S. R. Hirsch, D. J.Brooks, P. M. Grasby, Br. J. Psychiatr.172, 316 (1998).

9. K. Hadland et al., Soc. Neurosci. Abstr. 25, 1893(1999).

10. Statistical, Parametric Mapping (Wellcome Depart-ment of Cognitive Neurology, London, 1999). Statis-tical parametric maps, SPM{t}s, were calculated forcondition-specific effects within a general linearmodel. All modeled events and epochs were con-volved by a canonical hemodynamic response func-tion. Low-frequency changes in BOLD signal overtime were modeled with discrete cosine functions ofperiodicity ranging from 400 to 2400 s. The datawere temporally smoothed by a canonical hemody-namic response function and by intrinsic temporalautocorrelations modeled by a first-order autoregres-sion algorithm [G.K. Aguirre, E. Zarahn, M. D’Esposito,Neuroimage 5,199 (1998)]. Voxels were identified atwhich the probability of the observed condition-specific activation was less than 0.05, corrected formultiple comparisons (corresponding to t statistic.4.91). Contrasts discussed include the main effectseach of visual stimulus presentation, motor response,and selection against baseline, and the contrast ofworking memory delay versus an equivalent period incontrol trials (memory versus nonmemory epochs).

11. M. Petrides and D. N. Pandya, in Handbook of Neu-ropsychology, J. Grafman and F. Boller, Eds. (Elsevier,Amsterdam, 1995), vol. 9, pp. 17–58.

12. G. Rajkowska and P. S. Goldman-Rakic, Cereb. Cortex5, 307 (1995).

13. For any voxel, the sum of all modeled covariatesmultiplied by their empirically derived parameter es-timates provides the best fit to the data for eachparticipant. These fitted data were temporally re-aligned to the start of working memory trials andaveraged across participants for each length of work-ing memory trial. These data were scaled to representbest-fitted percentage change in the BOLD signal (zaxis) over time (x axis), separately for each length ofmemory ( y axis) (Fig. 3, C through D, and Fig. 4, Cthrough D).

14. B. R. Postle and M. D’Esposito, J. Cogn. Neurosci. 11,585 (1999). The time course of activation is shown infigs. 2 and 6.

15. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,Nature 386, 608 (1997).

16. A. Belger et al., Hum. Brain Mapp. 6, 14 (1998).17. B. Luna et al., Cereb. Cortex 8, 40 (1998).18. A. C. Nobre et al., Brain 120, 515 (1997).19. T. Sawaguchi and I. Yamane, J. Neurophysiol. 82,

2070 (1999 .20. M. V. Chafee and P. S. Goldman-Rakic, J. Neuro-

physiol. 79, 2919 (1998).

21. H. Niki and M. Watanabe, Brain Res. 105, 79(1976).

22. S. Funahashi, M. V. Chafee, P. S. Goldman-Rakic,Nature 365, 753 (1993).

23. J. Quintana and J. M. Fuster, Cereb. Cortex 9, 213(1999).

24. S. Funahashi, C. J. Bruce, P. S. Goldman-Rakic, J. Neu-rophysiol. 61, 331 (1989).

25. S. Kojima and P. S. Goldman-Rakic, Brain Res. 291,229 (1984).

26. A. M. Owen et al., Eur. J. Neurosci. 11, 567 (1999).27. M. Petrides, B. Alivisatos, A. C. Evans, E. Meyer, Proc.

Natl. Acad. Sci. U.S.A. 90, 873 (1993).28. A. M. Owen, A. C. Evans, M. Petrides, Cereb. Cortex 6,

31 (1996).29. E. K. Miller, Neuron 22, 15 (1999).

30. R. Levy and P. S. Goldman-Rakic, J. Neurosci. 19,5149 (1999).

31. A. Diamond and P. S. Goldman-Rakic, Exp. Brain Res.74, 24 (1989).

32. G. K. Aguirre, E. Zarahn, M. D’Esposito, Neuroimage 8,360 (1998).

33. Normal anatomic space was defined according to J.Talairach and P. Tournoux, A Co-planar StereotacticAtlas of the Human Brain (Thieme, Stuttgart, Germa-ny, 1988), using the Montreal Neurological Institutetemplate.

34. K. J. Friston, J. Ashburner, J.-B. Poline, C. D. Frith,R. S. J. Frackowiak, Hum. Brain Mapp. 2, 165 (1995).

35. Supported by the Wellcome Trust.

21 January 2000; accepted 31 March 2000

Generalized Potential of AdultNeural Stem Cells

Diana L. Clarke,1 Clas B. Johansson,1,2 Johannes Wilbertz,1

Biborka Veress,1 Erik Nilsson,1 Helena Karlstrom,1

Urban Lendahl,1 Jonas Frisen1*

The differentiation potential of stem cells in tissues of the adult has beenthought to be limited to cell lineages present in the organ from which they werederived, but there is evidence that some stem cells may have a broader dif-ferentiation repertoire. We show here that neural stem cells from the adultmouse brain can contribute to the formation of chimeric chick and mouseembryos and give rise to cells of all germ layers. This demonstrates that an adultneural stem cell has a very broad developmental capacity and may potentiallybe used to generate a variety of cell types for transplantation in differentdiseases.

Multicellular organisms are formed from asingle totipotent stem cell. As this cell and itsprogeny undergo cell divisions, the potentialof the cells becomes restricted, and they spe-cialize to generate cells of a certain lineage.In several tissues a stem cell population ismaintained in the adult organ, and it maygenerate new cells continuously or in re-sponse to injury. The adult brain and spinalcord retain neural stem cells that can generateneurons, astrocytes, and oligodendrocytes (1–5). Two stem cell populations have recentlybeen identified in the adult central nervoussystem—ependymal cells (6) and subven-tricular zone astrocytes (7)—although it isnot yet clear whether these two cell typesrepresent independent populations or whetherthey share a lineage relationship (3, 8). Thesecells can be cultured as clonal cell aggregatesreferred to as neurospheres (9).

Most of the available data indicate thatprogeny produced by nervous system stem cellsis limited to neural cell fates (1–5). It is, how-ever, possible that the cellular fates generatedby adult neural stem cells are restricted becauseof the limitations imposed on them by the par-

ticular environment in which they have beenevaluated. In line with this, neural stem cellsisolated from the adult forebrain were recentlyshown to be capable of repopulating the hema-topoietic system and produce blood cells inirradiated adult mice (10). However, becausethis method of addressing the potency of neuralstem cells fell within the limits of the hemato-poietic system, their repertoire of progeny wasstill restricted. We have expanded the questionof the differentiation potential of adult neuralstem cells by exposing them to different induc-tive environments.

Embryonic stem (ES) cells are totipotentand can be induced to differentiate into avariety of cell types when cultured as embry-oid bodies (11). We reasoned that inductivesignals for differentiation to diverse lineagesmust be present in these cultures. To evaluatethe capacity of inductive signals from EScells to guide the differentiation of neuralstem cells, we cultured adult neural stem cellstogether with embryoid bodies. The neuralstem cells, derived from ROSA26 mice (12),express b-galactosidase (b-Gal), enablingidentification of their progeny by X-Gal his-tochemistry or with antibodies against b-Gal(13). Moreover, ROSA26 cells express theneomycin resistance gene, which allowed usto later eliminate the G418-sensitive ES cellsfrom the cocultures and specifically study theremaining resistant neural stem cell–derived

1Department of Cell and Molecular Biology, MedicalNobel Institute, and 2Department of Neuroscience,Karolinska Institute, SE-171 77 Stockholm, Sweden.

*To whom correspondence should be addressed. E-mail jonas.frisen@cmb.ki.se

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cells. When cultured with embryoid bodies,neural stem cell progeny was frequentlyfound to display immunoreactivity fordesmin (Fig. 1, A and B), an intermediatefilament protein expressed by myocytes (14).Moreover, many of the neural stem cell–derived cells fused to form muscle cell–likesyncytia and showed immunoreactivity to themyocyte protein, myosin heavy chain (15)(Fig. 1, C and D). These cells did not displayany signs of cellular transformation. Neuralstem cells cultured under the same condi-tions, but in the absence of ES cells, did notexpress these markers, nor did they formsyncytia. We did not find evidence for differ-entiation to endodermal cell fates by immu-nohistochemistry with an antibody against anendoderm-specific epitope [TROMA-1 (16)].This observation is consistent with the factthat endodermal differentiation is rare in em-bryoid body cultures, in contrast to musclecell differentiation, which is commonly ob-served. These data demonstrate that adultneural stem cell–derived cells can adopt amuscle fate in vitro. This finding is substan-tiated by reports of myocyte generation in theembryonic mouse neural tube as well as froma medulloblastoma cell line (17, 18).

To analyze the differentiation potential ofadult neural stem cells in vivo, we assayedtheir ability to contribute to the formation ofvarious tissues by introducing them into theearly embryonic environment and observingthe fate of their progeny. The lineage restric-tion of rodent neural crest cells was previous-ly tested by transplantation to stage 18 chickembryos (19, 20). We injected adult mousebrain neural stem cells into the amniotic cav-ity of stage 4 chick embryos (21). We rea-soned that this may allow some neural stemcells to integrate into the primitive ectodermthat faces the amniotic cavity and to becomedistributed in the definitive ectoderm,endoderm, and mesoderm during gastrulation(Fig. 2, A and B). The cells would then beexposed to various inductive environments inthe different germ layers. Of the embryos thatsurvived the injection of the neurospheres(26%), 24 out of 109 were chimeric andcontained lacZ-positive cells derived fromthe adult neural stem cells. No chimeric em-bryos were derived from injections of disso-ciated neurosphere cells. The specificity ofthe X-Gal staining in chimeric embryos wassupported by overlapping immunohistochem-ical labeling with antisera against b-Gal (21).The murine origin of these cells was furtherconfirmed by overlapping immunoreactivityto the mouse-specific epitope H-2Kb (21)(Fig. 2F). In addition to the nervous system,where reproducibly a high degree of chimer-ism was seen, lacZ-expressing cells were fre-quently found in mesodermal derivativessuch as the mesonephros and notochord, aswell as in epithelial cells of the liver and

intestine, which are of endodermal origin(Table 1 and Fig. 2). In the tissues containinglacZ-expressing cells, there was a mosaicpattern of labeling with a varying proportionof neural stem cell–derived cells (Fig. 2). ThelacZ-expressing cells had indistinguishablemorphology from surrounding host cells andexpressed markers normally present in cellsof the particular tissue, for example, Pax2 inmesonephric tubule cells (Fig. 2G) and kera-tin in epidermal cells (21).

To test whether a single neural stem cellmay have the potential to generate progenythat can differentiate into various cell types,we established clonal cultures by transferringsingle cells from dissociated neurospheres tomicrowells with a micropipette (21). Neuro-

spheres derived from single-cell cultureswere tested in the chick assay and were foundto have the same broad differentiation poten-tial as described above, demonstrating that asingle adult neural stem cell has the potentialto generate progeny of various lineages. Tospecifically test the differentiation potentialof an identified neural stem cell, we culturedcells from the lateral ventricular wall of ani-mals that had received an injection of thefluorescent dye DiI (1,19-dioctadecyl-3,3,39,39-tetramethylindocarbocyanine per-chlorate) (21). In such cultures, DiI-labeledneurospheres from ependymal cells (6) wereisolated with a micropipette and injected intothe amniotic cavity of chick embryos. Theseependyma-derived neural stem cells showed

Fig. 1. Generation of myo-cytes from adult neuralstem cells. Neural stem cellclones from ROSA26 micewere cultured with embry-oid bodies to induce differ-entiation; the ES cells weresubsequently eliminatedby G418 selection. A sub-population of b-Gal–im-munoreactive neural stemcell progeny (A) is elongat-ed and shows immunore-activity for the muscle cellmarker desmin (B). Someneural stem cell–derivedcells are myosin heavychain–immunoreactive andshow varying degrees offusion and syncytia forma-tion (C and D). Nuclei arevisualized with blue Hoechst stain in (D). Bars, 20 mm (B and C) and 50 mm (D).

Fig. 2. Adult neuralstem cells contributeto the formation ofseveral organs in chickembryos. (A) Whole-mount X-Gal stainingof a stage 8 chick em-bryo, visualizing scat-tered blue neural stemcell–derived cells. Theline indicates theplane of section of thesame embryo shownin (B). Neuroectoderm(ne), mesoderm (m),and endoderm (e) areindicated. (C) Thetrunk region of acleared highly chimer-ic stage 23 embryo. Across section of theembryo in (C) (planeof section indicated byline) is shown in (D).Liver (li), mesonephros (mn), notochord (n), and spinal cord (sc) are indicated. (E) Neural stemcell– derived cells visualized with an antibody against the mouse-specific epitope H-2Kb

intermingled with host cells in the liver of a stage 23 chick embryo. (F) The epithelium of thestomach shows H-2Kb immunoreactivity (brown) and X-Gal staining (blue). (G) Cytoplasmaticexpression of lacZ in mesonephric tubule cells (blue) show nuclear Pax2 immunoreactivity (red,high magnification of area in box). Bars, 250 mm (A and D), 50 mm (B), 500 mm (C), and 25mm (E to G).

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the same broad differentiation potential asdescribed above (16).

Chimeric mice can be generated by aggre-gation of ES cells with morulae or injectioninto blastocysts, which are then implanted inpseudopregnant foster mothers (22). In addi-tion, chimeric mice have been generated fromblastocysts injected with adult hematopoieticstem cells (23). This study demonstrated thatadult bone marrow–derived stem cells canintegrate in the early embryonic environment,although only their potential to contribute tothe hematopoietic system was assessed in thisstudy (23). To test the ability of adult neuralstem cells to contribute to the generation oftissues in the developing mouse embryo, dis-sociated cells from a neurosphere were ag-gregated with morulae and allowed to contin-ue their development in vitro to the earlyblastocyst stage (21). Many lacZ–positivecells integrated into the trophoblast layer, butonly rarely were cells found in the inner cellmass of the developing blastocyst (Fig. 3A).More efficient contribution of neural stemcells to the inner cell mass was acquired bymicroinjecting the cells directly into earlyblastocysts. Aggregated morulae and injectedblastocysts were transferred to foster mothersand allowed to develop until embryonic day11. Analysis of lacZ expression in embryosby X-Gal histochemistry, immunohistochem-istry, and reverse transcription–polymerasechain reaction (RT-PCR) (21) (Figs. 3 and 4)revealed that 1% (6 out of 600) of embryosderived from aggregation or injection of dis-sociated cells and 12% (11 out of 94) ofembryos generated by injection of a neuro-sphere contained cells derived from adultneural stem cells. In all litters, most of theembryos completely lacked lacZ-expressingcells, and among the positive embryos, therewas a varying degree of mosaicism. Chimericembryos were of similar size as nonchimericembryos and did not display any overt ana-tomical abnormalities (Fig. 3C). The speci-ficity of the X-Gal staining in chimeric em-bryos was confirmed by overlapping immu-nohistochemical labeling with antiseraagainst b-Gal (Fig. 4, A and B). In severalembryos derived from injected blastocysts,extensive contribution of the ROSA26-de-rived neural stem cells was seen in the em-bryonic central nervous system, heart, liver,intestine, and other tissues (Figs. 3C and 4and Table 1). lacZ-expressing cells expressedmarkers typical for the tissue in which theyhad incorporated, for example, desmin inheart, cytokeratin 20 in intestinal epithelium,and albumin in liver (Fig. 4). Perhaps themost striking indication that these cells maytake on functions appropriate for the newlyformed tissue was the finding of beatinghearts of apparent normal anatomy in chimer-ic mouse embryos having a very large con-tribution of neural stem cell–derived cells in

the heart. These data demonstrate that adultneural stem cells can integrate into the devel-oping chick and mouse embryo, give rise toembryonic cells of various fates, and contrib-

ute to the generation of tissues and organs ofall germ layers. Thus, the present study fo-cuses on the integration and differentiation ofadult neural stem cells into embryonic tissues

Fig. 3. Generation of chimericmouse embryos. (A) X-Gal stain-ing of a blastocyst developed invitro from a morula aggregationexperiment shows neural stemcell–derived cells (blue) in theinner cell mass. (B) RT-PCR de-tection of b-Gal mRNA inROSA26-derived adult neuralstem cells (1), amnion (a), headregion (h), trunk (t), and caudalpart (c) of a wild-type embryo(Control) and embryos generat-ed by blastocyst injection ofROSA26 neural stem cells [In-jected, embryos other thanshown in (C)]. Primers for theL19 gene were included in allreactions as an internal control.(C) X-Gal staining of an embry-onic day 11 wild-type embryo(left) and a mouse embryo gen-erated from a blastocyst intowhich adult neural stem cellswere injected (right). Some endogenous staining is seen in the area of the otic vesicle in thewild-type embryo. Bars, 20 mm (A) and 1 mm (C).

Fig. 4. Contribution of adult neural stem cells to the formation of mesodermal and endodermaltissues in the mouse. (A and B) Adjacent cross sections through the abdominal cavity of alow-degree embryonic day 11 chimeric embryo, displaying X-Gal labeling (A) and b-Gal immuno-reactivity (B) in epithelial cells of the stomach (s) and intestine (i). (C) Immunoreactivity for theepithelial marker cytokeratin 20 in lacZ-expressing adult neural stem cell–derived cells (D). (E)Cross sections of a highly chimeric embryo labeled with an antibody against b-Gal, demonstratingabundant contribution of adult neural stem cell progeny in liver and heart. (F) Neural stemcell–derived cells in the heart (b-Gal immunoreactivity, green) of another chimeric embryo alsoshow immunoreactivity for the myocyte marker desmin (red). In the liver, neural stem cell progeny( X-Gal labeling, blue) are immunoreactive for the hepatocyte-specific protein albumin (red) (G). Adetail from (G) is shown at higher magnification in the inset. Arrow in (G) indicates the right lungbud. Bars, 100 mm (B and E), 50 mm (D and F), and 10 mm (G).

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and raises many intriguing questions regard-ing the long-term commitment and survivalof these cells.

Although we reproducibly found neuralstem cell progeny in various organs in chickand mouse embryos, other tissues containedno lacZ-expressing cells. For example, wedid not detect any contribution to the hema-topoietic system in the models we used. This

is intriguing because the adult neural stemcells can differentiate along this lineage aftertransplantation to irradiated adult mice (10).It is well established from ES cell studies thatthe strain background of the ES and host cellshave a large influence on the degree of chi-merism in specific tissues and that certainstrain combinations result in no or very lowchimerism in certain organs (24). Thus, al-though the ES cells are totipotent, they do notdisplay their full potential in certain situa-tions. In line with this, it appears that theneural stem cells may have a broader differ-entiation potential than revealed in the chickand mouse embryo assays.

In addition to the demonstration of bloodcell generation by neural stem cells (10),there have recently been indications that oth-er stem cell populations may not be restrictedto generating cell types specific for the tissuein which they reside. Thus, marrow stromalcells transplanted to the brain can generateastrocytes (25). Moreover, hematopoieticstem cells can give rise to myocytes, andmuscle progenitor cells can generate bloodcells (26, 27). Together with the data present-ed here, these studies suggest that stem cellsin different adult tissues may be more similarthan previously thought and perhaps in somecases have a developmental repertoire closeto that of ES cells.

References and Notes1. R. McKay, Science 276, 66 (1997).2. S. Weiss and D. van der Kooy, J. Neurobiol. 36, 307

(1998).3. S. Momma, C. B. Johansson, J. Frisen, Curr. Opin.

Neurobiol. 10, 45 (2000).4. L. S. Shiabuddin, T. D. Palmer, F. H. Gage, Mol. Med.

Today 5, 474 (1999).5. S. Temple and A. Alvarez-Buylla, Curr. Opin. Neuro-

biol. 9, 135 (1999).6. C. B. Johansson et al., Cell 96, 25 (1999).

7. F. Doetsch, I. Caille, D. A. Lim, J. M. Garcia-Verdugo, A.Alvarez-Buylla, Cell 97, 703 (1999).

8. B. A. Barres, Cell 97, 667 (1999).9. B. A. Reynolds and S. Weiss, Science 255, 1707

(1992).10. C. R. Bjornson, R. L. Rietze, B. A. Reynolds, M. C. Magli,

A. L. Vescovi, Science 283, 534 (1999).11. G. M. Keller, Curr. Opin. Cell Biol. 7, 862 (1995).12. G. Friedrich and P. Soriano, Genes Dev. 5, 1513

(1991).13. Neurosphere cultures were established as described

(6, 21).14. E. Lazarides and B. D. Hubbard, Proc. Natl. Acad. Sci.

U.S.A. 73, 4344 (1976).15. D. Bader, T. Masaki, D. A. Fischman, J. Cell Biol. 95,

763 (1982).16. D. L. Clarke et al., data not shown.17. S. Tajbakhsh et al., Neuron 13, 813 (1994).18. N. L. Valtz, T. E. Hayes, T. Norregard, S. M. Liu, R. D.

McKay, New Biol. 3, 364 (1991).19. S. J. Morrison, P. M. White, C. Zock, D. J. Anderson,

Cell 96, 737 (1999).20. P. M. White and D. J. Anderson, Development 126,

4351 (1999).21. A detailed description of methods and additional

figures can be found at Science Online at www.sciencemag.org/feature/data/1047254.shl. .

22. A. L. Joyner, Ed., Gene Targeting. A Practical Approach(Oxford Univ. Press, Oxford, 1993).

23. H. Geiger, S. Sick, C. Bonifer, A. M. Muller, Cell 93,1055 (1998).

24. J. D. West, Curr. Top. Dev. Biol. 44, 21 (1999).25. G. C. Kopen, D. J. Prockop, D. G. Phinney, Proc. Natl.

Acad. Sci. U.S.A. 96, 10711 (1999).26. E. Gussoni et al., Nature 401, 390 (1999).27. K. A. Jackson, T. Mi, M. A. Goodell, Proc. Natl. Acad.

Sci. U.S.A. 96, 14482 (1999).28. We are indebted to J. Ericson, L. Philipson, and mem-

bers of our laboratory for helpful discussions andcomments on the manuscript. We are grateful to J.Ericson and J. Muhr for introducing us to chick em-bryo manipulations and for valuable advice. Sup-ported by the Swedish Medical Research Council,the Swedish Cancer Society, the Swedish Founda-tion for Strategic Research, EU Biotech BIO4-98-0159, the Karolinska Institute, the Swedish MedicalSociety, Bjorklunds fond, Ostermans stiftelse, Hag-bergs stiftelse, the Swedish Parkinson Foundation,NeuroNova AB, and Kapten Arthur Erikssons fond.D.L.C. was supported by a Wenner-Gren postdoctoralfellowship.

19 November 1999; accepted 25 April 2000

Table 1. Frequency of chimerism in various tissuesin chick and mouse embryos containing neuralstem cell progeny.

Tissue Chick (%)Mouse

(%)

EctodermalForebrain 71 (17/24) 53 (9/17)Midbrain 71 (17/24) 53 (9/17)Hindbrain 71 (17/24) 53 (9/17)Spinal cord 96 (23/24) 59 (10/17)Epidermis 79 (19/24) 65 (11/17)

MesodermalNotochord 96 (23/24) 94 (16/17)Mesonephric

epithelium92 (22/24) 71 (12/17)

Mesonephricmesenchyme

92 (22/24) 71 (12/17)

Somites 71 (17/24) 71 (12/17)Heart

muscle38 (9/24) 59 (10/17)

EndodermalLung

epithelium45 (9/20) 59 (10/17)

Stomachepithelium

83 (20/24) 82 (14/17)

Stomachwall

83 (20/24) 71 (12/17)

Intestinalepithelium

96 (23/24) 76 (13/17)

Intestinalwall

83 (20/24) 65 (11/17)

Liver 92 (22/24) 94 (16/17)

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DOI: 10.1126/science.288.5471.1660, 1660 (2000);288 Science

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