The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue
Open accessAbstract
In the developing neural retina (NR), multipotent stem cells within the ciliary margin (CM) contribute to de novo retinal tissue growth. We recently reported the ability of human embryonic stem cells (hESCs) to self-organize stratified NR using a three-dimensional culture technique. Here we report the emergence of CM-like stem cell niches within human retinal tissue. First, we developed a culture method for selective NR differentiation by timed BMP4 treatment. We then found that inhibiting GSK3 and FGFR induced the transition from NR tissue to retinal pigment epithelium (RPE), and that removing this inhibition facilitated the reversion of this RPE-like tissue back to the NR fate. This step-wise induction-reversal method generated tissue aggregates with RPE at the margin of central-peripherally polarized NR. We demonstrate that the NR–RPE boundary tissue further self-organizes a niche for CM stem cells that functions to expand the NR peripherally by de novo progenitor generation. The ciliary margin of the eye functions as a source of multipotent progenitor cells in certain organisms but whether it plays this role in humans has not been easy to study. Here the authors culture human embryonic stem cells that self-organize into retinal tissue, and show that ciliary margin-like growth zones emerge from the developing human retinal tissue and contain stem cell niches.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055
Self-citationSelf-organizing optic-cup morphogenesis in three-dimensional culture
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011) · Nature · doi:10.1038/nature09941 · Cited by 2,001
Self-citationSelf-formation of optic cups and storable stratified neural retina from human ESCs
Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., Saito, K., Yonemura, S., Eiraku, M., & Sasai, Y. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.009 · Cited by 1,447
Self-citationRetinal Stem Cells in the Adult Mammalian Eye
Tropepe, V., Coles, B. L. K., Chiasson, B. J., Horsford, D. J., Elia, A. J., McInnes, R. R., & van der Kooy, D. (2000) · Science · doi:10.1126/science.287.5460.2032 · Cited by 1,081
Cell differentiation in the retina of the mouse
Young, R. W. (1985) · The Anatomical Record · doi:10.1002/ar.1092120215 · Cited by 1,071
Vertebrate neural cell-fate determination: Lessons from the retina
Livesey, F. J., & Cepko, C. L. (2001) · Nature Reviews Neuroscience · doi:10.1038/35053522 · Cited by 947
The Rx homeobox gene is essential for vertebrate eye development
Mathers, P. H., Grinberg, A., Mahon, K. A., & Jamrich, M. (1997) · Nature · doi:10.1038/42475 · Cited by 712
Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development
Furuta, Y., Piston, D. W., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.11.2203 · Cited by 709
Efficient generation of retinal progenitor cells from human embryonic stem cells
Lamba, D. A., Karl, M. O., Ware, C. B., & Reh, T. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601990103 · Cited by 689
Early Eye Development in Vertebrates
Chow, R. L., & Lang, R. A. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.255 · Cited by 642
Osakada, F., Ikeda, H., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., Akaike, A., Sasai, Y., & Takahashi, M. (2008) · Nature Biotechnology · doi:10.1038/nbt1384 · Cited by 633
Self-citationREGIONALIZATION OF THE PROSENCEPHALIC NEURAL PLATE
Rubenstein, J. L. R., Shimamura, K., Martinez, S., & Puelles, L. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.445 · Cited by 550
Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.07.002 · Cited by 486
Cytosystems dynamics in self-organization of tissue architecture
Sasai, Y. (2013) · Nature · doi:10.1038/nature11859 · Cited by 483
Self-citationKawasaki, H., Suemori, H., Mizuseki, K., Watanabe, K., Urano, F., Ichinose, H., Haruta, M., Takahashi, M., Yoshikawa, K., Nishikawa, S.-I., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032662199 · Cited by 477
Self-citationMeyer, J. S., Howden, S. E., Wallace, K. A., Verhoeven, A. D., Wright, L. S., Capowski, E. E., Pinilla, I., Martin, J. M., Tian, S., Stewart, R., et al. (2011) · Stem Cells · doi:10.1002/stem.674 · Cited by 469
Facile isolation and the characterization of human retinal stem cells
Coles, B. L. K., Angénieux, B., Inoue, T., Del Rio-Tsonis, K., Spence, J. R., McInnes, R. R., Arsenijevic, Y., & van der Kooy, D. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401596101 · Cited by 412
Lamba, D. A., McUsic, A., Hirata, R. K., Wang, P.-R., Russell, D., & Reh, T. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008763 · Cited by 394
Liu, I. S. C., Chen, J.-D., Ploder, L., Vidgen, D., van der Kooy, D., Kalnins, V. I., & Mclnnes, R. R. (1994) · Neuron · doi:10.1016/0896-6273(94)90354-9 · Cited by 383
Foxg1 Suppresses Early Cortical Cell Fate
Hanashima, C., Li, S. C., Shen, L., Lai, E., & Fishell, G. (2004) · Science · doi:10.1126/science.1090674 · Cited by 380
Gonzalez-Cordero, A., West, E. L., Pearson, R. A., Duran, Y., Carvalho, L. S., Chu, C. J., Naeem, A., Blackford, S. J. I., Georgiadis, A., Lakowski, J., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2643 · Cited by 373
Generation of Rx + /Pax6 + neural retinal precursors from embryonic stem cells
Ikeda, H., Osakada, F., Watanabe, K., Mizuseki, K., Haraguchi, T., Miyoshi, H., Kamiya, D., Honda, Y., Sasai, N., Yoshimura, N., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500010102 · Cited by 335
Self-citationNagai, T., Aruga, J., Takada, S., Günther, T., Spörle, R., Schughart, K., & Mikoshiba, K. (1997) · Developmental Biology · doi:10.1006/dbio.1996.8449 · Cited by 318
Basic fibroblast growth factor induces retinal regeneration in vivo
Park, C. M., & Hollenberg, M. J. (1989) · Developmental Biology · doi:10.1016/0012-1606(89)90089-4 · Cited by 296
Graw, J. (2010) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)90010-0 · Cited by 273
Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation
Wataya, T., Ando, S., Muguruma, K., Ikeda, H., Watanabe, K., Eiraku, M., Kawada, M., Takahashi, J., Hashimoto, N., & Sasai, Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803078105 · Cited by 270
Self-citationLawrence, J. M., Singhal, S., Bhatia, B., Keegan, D. J., Reh, T. A., Luthert, P. J., Khaw, P. T., & Limb, G. A. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0724 · Cited by 269
Adult Human RPE Can Be Activated into a Multipotent Stem Cell that Produces Mesenchymal Derivatives
Salero, E., Blenkinsop, T. A., Corneo, B., Harris, A., Rabin, D., Stern, J. H., & Temple, S. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2011.11.018 · Cited by 258
Actomyosin Is the Main Driver of Interkinetic Nuclear Migration in the Retina
Norden, C., Young, S., Link, B. A., & Harris, W. A. (2009) · Cell · doi:10.1016/j.cell.2009.06.032 · Cited by 253
From Progenitors to Differentiated Cells in the Vertebrate Retina
Agathocleous, M., & Harris, W. A. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113259 · Cited by 246
Multipotential stem cells and progenitors in the vertebrate retina
Reh, T. A., & Levine, E. M. (1998) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199808)36:2<206::aid-neu8>3.0.co;2-5 · Cited by 229
Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling
Yasumoto, K.-I. (2002) · The EMBO Journal · doi:10.1093/emboj/21.11.2703 · Cited by 228
Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells
Cicero, S. A., Johnson, D., Reyntjens, S., Frase, S., Connell, S., Chow, L. M. L., Baker, S. J., Sorrentino, B. P., & Dyer, M. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901596106 · Cited by 223
Wnt2b controls retinal cell differentiation at the ciliary marginal zone
Kubo, F., Takeichi, M., & Nakagawa, S. (2003) · Development · doi:10.1242/dev.00244 · Cited by 214
Liu, H., Mohamed, O., Dufort, D., & Wallace, V. A. (2003) · Developmental Dynamics · doi:10.1002/dvdy.10315 · Cited by 203
Guillemot, F., & Cepko, C. L. (1992) · Development · doi:10.1242/dev.114.3.743 · Cited by 193
Dyer, M. A., & Cepko, C. L. (2000) · Development · doi:10.1242/dev.127.16.3593 · Cited by 192
Baye, L. M., & Link, B. A. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2754-07.2007 · Cited by 186
Jadhav, A. P., Cho, S.-H., & Cepko, C. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608155103 · Cited by 178
Westenskow, P., Piccolo, S., & Fuhrmann, S. (2009) · Development · doi:10.1242/dev.032136 · Cited by 175
The retinal pigment epithelium: An important player of retinal disorders and regeneration
Chiba, C. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2013.07.009 · Cited by 172
p27Kip1 Regulates Cell Cycle Withdrawal of Late Multipotent Progenitor Cells in the Mammalian Retina
Levine, E. M., Close, J., Fero, M., Ostrovsky, A., & Reh, T. A. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9622 · Cited by 171
Wnt signaling in eye organogenesis
Fuhrmann, S. (2008) · Organogenesis · doi:10.4161/org.4.2.5850 · Cited by 168
Rowan, S., Chen, C.-M. A., Young, T. L., Fisher, D. E., & Cepko, C. L. (2004) · Development · doi:10.1242/dev.01300 · Cited by 162
Fujimura, N., Taketo, M. M., Mori, M., Kořínek, V., & Kozmík, Z. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.07.002 · Cited by 149
Lineage in the vertebrate retina
Cayouette, M., Poggi, L., & Harris, W. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.08.003 · Cited by 138
Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo
Müller, F. W., Rohrer, H., & Vogel‐Höpker, A. (2007) · Development · doi:10.1242/dev.02884 · Cited by 112
Bhatia, B., Singhal, S., Lawrence, J. M., Khaw, P. T., & Limb, G. A. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.04.005 · Cited by 111
Liu, W., Lagutin, O. V., Swindell, E. C., Jamrich, M., & Oliver, G. C. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43219 · Cited by 109
Zhu, Y., Carido, M., Meinhardt, A., Kurth, T., Karl, M., Ader, M., & Tanaka, E. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054552 · Cited by 107
Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin
Dale, J. K., Sattar, N., Heemskerk, J., Clarke, J. D. W., Placzek, M., & Dodd, J. (1999) · Development · doi:10.1242/dev.126.2.397 · Cited by 105
Diep, D. B., Hoen, N., Backman, M., Machoň, O., & Krauss, S. J. K. (2004) · Developmental Brain Research · doi:10.1016/j.devbrainres.2004.09.008 · Cited by 97
Fate Restriction and Multipotency in Retinal Stem Cells
Centanin, L., Höckendorf, B., & Wittbrodt, J. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.11.004 · Cited by 96
The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate eye
Fischer, A. J., Bosse, J. L., & El‐Hodiri, H. M. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.08.018 · Cited by 96
Retinal regeneration in amphibians
Mitashov, V. I. (1997) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9449466 · Cited by 75
Martínez, G., Jeréz, A. A., Martín‐Nieto, J., & Cuenca, N. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21860 · Cited by 71
Expression of photoreceptor-associated molecules during human fetal eye development.
O’Brien, K. M. B., Schulte, D., & Hendrickson, A. E. (2003) · PubMed · Cited by 64
Temporal progression of hypothalamic patterning by a dual action of BMP
Ohyama, K., Das, R. M., & Placzek, M. (2008) · Development · doi:10.1242/dev.027078 · Cited by 52
Trimarchi, J. M., Cho, S., & Cepko, C. L. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21973 · Cited by 47
Kubo, F., & Nakagawa, S. (2009) · Development · doi:10.1242/dev.029272 · Cited by 44
Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina
Larsen, K. B., Lutterodt, M. C., Rath, M. F., & Møller, M. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.04.004 · Cited by 43
Yamaguchi, Y., Watanabe, T., Hirakata, A., & Hida, T. (2006) · Cell and Tissue Research · doi:10.1007/s00441-005-0122-z · Cited by 42
Adult Retinal Stem Cells Revisited
Bhatia, B., Singhal, S., Jayaram, H., Khaw, P. T., & Limb, G. A. (2010) · The Open Ophthalmology Journal · doi:10.2174/1874364101004010030 · Cited by 39
Ali, R. R., & Sowden, J. C. (2011) · Nature · doi:10.1038/472042a · Cited by 32
Stemness or Not Stemness? Current Status and Perspectives of Adult Retinal Stem Cells
Locker, M., Borday, C., & Perron, M. (2009) · Current Stem Cell Research & Therapy · doi:10.2174/157488809788167382 · Cited by 30
Generation and clonal isolation of retinal stem cells from human embryonic stem cells
Clarke, L., Ballios, B. G., & van der Kooy, D. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08123.x · Cited by 29
Induced Pluripotent Stem Cell Technology for Generating Photoreceptors
Boucherie, C., Sowden, J. C., & Ali, R. R. (2011) · Regenerative Medicine · doi:10.2217/rme.11.37 · Cited by 27
Koso, H., Iida, A., Tabata, Y., Baba, Y., Satoh, S., Taketo, M. M., & Watanabe, S. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0303 · Cited by 9
Cited by
Progress and potential in organoid research
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182
Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Cowan, C. S., Renner, M., De Gennaro, M., Gross-Scherf, B., Goldblum, D., Hou, Y., Munz, M., Rodrigues, T. M., Krol, J., Szikra, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.013 · Cited by 654
Capowski, E. E., Samimi, K., Mayerl, S. J., Phillips, M. J., Pinilla, I., Howden, S. E., Saha, J., Jansen, A. D., Edwards, K. L., Jager, L. D., et al. (2018) · Development · doi:10.1242/dev.171686 · Cited by 311
Ogura, T., Sakaguchi, H., Miyamoto, S., & Takahashi, J. (2018) · Development · doi:10.1242/dev.162214 · Cited by 183
Pluripotent stem cell-derived retinal organoids for disease modeling and development of therapies
Kruczek, K., & Swaroop, A. (2020) · Stem Cells · doi:10.1002/stem.3239 · Cited by 148
Metadata
- Authors
- Kuwahara, A., Ozone, C., Nakano, T., Saito, K., Eiraku, M., & Sasai, Y.
- Venue
- Nature Communications
- Published
- 2015-02-19
- Volume
- 6
- Issue
- 1
- Pages
- 6286-6286
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2063288238
- Cited by
- 349
- References
- 68
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
