{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:34:36Z","timestamp":1773286476894,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether \u201csilent\u201d neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15\u201321 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies. Stem Cells \u00a02015;33:491\u2013502<\/jats:p>","DOI":"10.1002\/stem.1856","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T21:18:39Z","timestamp":1412025519000},"page":"491-502","source":"Crossref","is-referenced-by-count":22,"title":["Mouse Embryonic Stem Cell-Derived Cells Reveal Niches that Support Neuronal Differentiation in the Adult Rat Brain"],"prefix":"10.1093","volume":"33","author":[{"given":"Guadalupe","family":"Maya-Espinosa","sequence":"first","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Collazo-Navarrete","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Mill\u00e1n-Aldaco","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Palomero-Rivero","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilda","family":"Guerrero-Flores","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics and Molecular Physiology Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Drucker-Col\u00edn","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Covarrubias","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics and Molecular Physiology Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Guerra-Crespo","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology Instituto de Fisiolog\u00eda Celular, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,1,22]]},"reference":[{"key":"2022010913471976800_stem1856-bib-0001","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.conb.2010.04.010","article-title":"Signaling in adult neurogenesis","volume":"20","author":"Mu","year":"2010","journal-title":"Curr Opin Neurobiol"},{"key":"2022010913471976800_stem1856-bib-0002","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0896-6273(04)00111-4","article-title":"For the long run: Maintaining germinal niches in the adult brain","volume":"41","author":"Alvarez-Buylla","year":"2004","journal-title":"Neuron"},{"key":"2022010913471976800_stem1856-bib-0003","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1523\/JNEUROSCI.22-02-00437.2002","article-title":"Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents","volume":"22","author":"Gritti","year":"2002","journal-title":"J Neurosci"},{"key":"2022010913471976800_stem1856-bib-0004","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nm747","article-title":"Neuronal replacement from endogenous precursors in the adult brain after stroke","volume":"8","author":"Arvidsson","year":"2002","journal-title":"Nat Med"},{"key":"2022010913471976800_stem1856-bib-0005","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/ana.10393","article-title":"Rat forebrain neurogenesis and striatal neuron replacement after focal stroke","volume":"52","author":"Parent","year":"2002","journal-title":"Ann Neurol"},{"key":"2022010913471976800_stem1856-bib-0006","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature00900","article-title":"Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease","volume":"418","author":"Kim","year":"2002","journal-title":"Nature"},{"issue":"Pt 3","key":"2022010913471976800_stem1856-bib-0007","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1093\/brain\/awm340","article-title":"Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson's disease","volume":"131","author":"O'Keeffe","year":"2008","journal-title":"Brain"},{"key":"2022010913471976800_stem1856-bib-0008","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/1531-8249(199912)46:6<867::AID-ANA9>3.0.CO;2-Z","article-title":"Adult-derived neural precursors transplanted into multiple regions in the adult brain","volume":"46","author":"Herrera","year":"1999","journal-title":"Ann Neurol"},{"key":"2022010913471976800_stem1856-bib-0009","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1111\/j.1460-9568.2005.04352.x","article-title":"Isolation and characterization of neural precursor cells from the Sox1-GFP reporter mouse","volume":"22","author":"Barraud","year":"2005","journal-title":"Eur J Neurosci"},{"key":"2022010913471976800_stem1856-bib-0010","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/scd.2011.0241","article-title":"Glial commitment of mesencephalic neural precursor cells expanded as neurospheres precludes their engagement in niche-dependent dopaminergic neurogenesis","volume":"21","author":"Baizabal","year":"2012","journal-title":"Stem Cells Dev"},{"key":"2022010913471976800_stem1856-bib-0011","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0092-8674(02)00835-8","article-title":"Directed differentiation of embryonic stem cells into motor neurons","volume":"110","author":"Wichterle","year":"2002","journal-title":"Cell"},{"key":"2022010913471976800_stem1856-bib-0012","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nn1301","article-title":"Differentiation of mouse embryonic stem cells into a defined neuronal lineage","volume":"7","author":"Bibel","year":"2004","journal-title":"Nat Neurosci"},{"key":"2022010913471976800_stem1856-bib-0013","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.1073\/pnas.0902396106","article-title":"Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells","volume":"106","author":"Friling","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"2022010913471976800_stem1856-bib-0014","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.celrep.2012.04.009","article-title":"Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions","volume":"1","author":"Kirkeby","year":"2012","journal-title":"Cell Rep"},{"key":"2022010913471976800_stem1856-bib-0015","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.stem.2012.01.021","article-title":"Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice","volume":"10","author":"Ma","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2022010913471976800_stem1856-bib-0016","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1006\/exnr.1997.6674","article-title":"Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation","volume":"149","author":"Deacon","year":"1998","journal-title":"Exp Neurol"},{"key":"2022010913471976800_stem1856-bib-0017","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1073\/pnas.022438099","article-title":"Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model","volume":"99","author":"Bjorklund","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010913471976800_stem1856-bib-0018","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ydbio.2008.09.024","article-title":"The embryonic midbrain directs neuronal specification of embryonic stem cells at early stages of differentiation","volume":"325","author":"Baizabal","year":"2009","journal-title":"Dev Biol"},{"key":"2022010913471976800_stem1856-bib-0019","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.neuroscience.2009.02.029","article-title":"Transforming growth factor-alpha induces neurogenesis and behavioral improvement in a chronic stroke model","volume":"160","author":"Guerra-Crespo","year":"2009","journal-title":"Neuroscience"},{"key":"2022010913471976800_stem1856-bib-0020","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos","year":"2005","edition":"5th"},{"key":"2022010913471976800_stem1856-bib-0021","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1089\/scd.2011.0593","article-title":"Zfhx1b induces a definitive neural stem cell fate in mouse embryonic stem cells","volume":"21","author":"Dang","year":"2012","journal-title":"Stem Cells Dev"},{"key":"2022010913471976800_stem1856-bib-0022","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nn1479","article-title":"Neuronal fate determinants of adult olfactory bulb neurogenesis","volume":"8","author":"Hack","year":"2005","journal-title":"Nat Neurosci"},{"key":"2022010913471976800_stem1856-bib-0023","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0168-0102(98)00002-9","article-title":"How simple is the organization of the olfactory glomerulus?: The heterogeneity of so-called periglomerular cells","volume":"30","author":"Kosaka","year":"1998","journal-title":"Neurosci Res"},{"key":"2022010913471976800_stem1856-bib-0024","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.1523\/JNEUROSCI.0700-08.2008","article-title":"A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb","volume":"28","author":"Brill","year":"2008","journal-title":"J Neurosci"},{"issue":"Suppl 1","key":"2022010913471976800_stem1856-bib-0025","doi-asserted-by":"crossref","first-page":"i78","DOI":"10.1093\/cercor\/bhp028","article-title":"Origin, early commitment, migratory routes, and destination of cannabinoid type 1 receptor-containing interneurons","volume":"19","author":"Morozov","year":"2009","journal-title":"Cereb Cortex"},{"key":"2022010913471976800_stem1856-bib-0026","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.1073\/pnas.1131955100","article-title":"Evidence for neurogenesis in the adult mammalian substantia nigra","volume":"100","author":"Zhao","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010913471976800_stem1856-bib-0027","doi-asserted-by":"crossref","first-page":"6639","DOI":"10.1523\/JNEUROSCI.22-15-06639.2002","article-title":"The adult substantia nigra contains progenitor cells with neurogenic potential","volume":"22","author":"Lie","year":"2002","journal-title":"J Neurosci"},{"key":"2022010913471976800_stem1856-bib-0028","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrn2147","article-title":"How widespread is adult neurogenesis in mammals?","volume":"8","author":"Gould","year":"2007","journal-title":"Nat Rev Neurosci"},{"key":"2022010913471976800_stem1856-bib-0029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/nbdi.1997.0137","article-title":"Neural precursor cells: Applications for the study and repair of the central nervous system","volume":"4","author":"Fisher","year":"1997","journal-title":"Neurobiol Dis"},{"key":"2022010913471976800_stem1856-bib-0030","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.neuroscience.2005.12.043","article-title":"Long-term fate of neural precursor cells following transplantation into developing and adult CNS","volume":"139","author":"Lepore","year":"2006","journal-title":"Neuroscience"},{"key":"2022010913471976800_stem1856-bib-0031","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1089\/scd.2012.0530","article-title":"Neural stem cells engrafted in the adult brain fuse with endogenous neurons","volume":"22","author":"Brilli","year":"2013","journal-title":"Stem Cells Dev"},{"key":"2022010913471976800_stem1856-bib-0032","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1002\/stem.1227","article-title":"Embryonic stem cell-derived neural stem cells fuse with microglia and mature neurons","volume":"30","author":"Cusulin","year":"2012","journal-title":"Stem Cells"},{"key":"2022010913471976800_stem1856-bib-0033","doi-asserted-by":"crossref","first-page":"6878","DOI":"10.1523\/JNEUROSCI.0254-07.2007","article-title":"A subpopulation of olfactory bulb GABAergic interneurons is derived from Emx1- and Dlx5\/6-expressing progenitors","volume":"27","author":"Kohwi","year":"2007","journal-title":"J Neurosci"},{"key":"2022010913471976800_stem1856-bib-0034","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1523\/JNEUROSCI.2870-06.2007","article-title":"Generation of distinct types of periglomerular olfactory bulb interneurons during development and in adult mice: Implication for intrinsic properties of the subventricular zone progenitor population","volume":"27","author":"Marchis","year":"2007","journal-title":"J Neurosci"},{"key":"2022010913471976800_stem1856-bib-0035","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0092-8674(04)00208-9","article-title":"Plasticity of adult stem cells","volume":"116","author":"Wagers","year":"2004","journal-title":"Cell"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.1856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.1856","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.1856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.1856","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/33\/2\/491\/42017747\/stmcls_33_2_491.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/33\/2\/491\/42017747\/stmcls_33_2_491.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:54:19Z","timestamp":1642560859000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/33\/2\/491-502\/6407094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,22]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,1,22]]},"published-print":{"date-parts":[[2015,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.1856","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,2,1]]},"published":{"date-parts":[[2015,1,22]]}}}