Directed differentiation of embryonic stem cells into bladder tissue

Siam Oottamasathien, Yong Qing Wang, Karin Williams, Omar E. Franco, Marcia L. Wills, John C. Thomas, Katrina Saba, Ali Reza Sharif-Afshar, John H. Makari, Neil A. Bhowmick, Romano T. DeMarco, Susan Hipkens, Mark Magnuson, John W. Brock, Simon W. Hayward, John C. Pope IV, Robert J. Matusik

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Manipulatable models of bladder development which interrogate specific pathways are badly needed. Such models will allow a systematic investigation of the multitude of pathologies which result from developmental defects of the urinary bladder. In the present communication, we describe a model in which mouse embryonic stem (ES) cells are directed to differentiate to form bladder tissue by specific interactions with fetal bladder mesenchyme. This model allows us to visualize the various stages in the differentiation of urothelium from ES cells, including the commitment to an endodermal cell lineage, with the temporal profile characterized by examining the induction of specific endodermal transcription factors (Foxa1 and Foxa2). In addition, final functional urothelial differentiation was characterized by examining uroplakin expression. It is well established that ES cells will spontaneously develop teratomas when grown within immunocompromised mouse hosts. We determined the specific mesenchymal to ES cell ratios necessary to dictate organ-specific differentiation while completely suppressing teratomatous growth. Embryonic mesenchyme is well established as an inductive tissue which dictates organ-specific programming of epithelial tissues. The present study demonstrates that embryonic bladder mesenchyme can also steer ES cells towards developing specific endodermal derived urothelium. These approaches allow us to capture specific stages of stem cell differentiation and to better define stem cell hierarchies.

Original languageEnglish (US)
Pages (from-to)556-566
Number of pages11
JournalDevelopmental Biology
Volume304
Issue number2
DOIs
StatePublished - Apr 15 2007

Fingerprint

Embryonic Stem Cells
Urinary Bladder
Mesoderm
Urothelium
Uroplakins
Stem Cells
Teratoma
Immunocompromised Host
Cell Lineage
Cell Differentiation
Transcription Factors
Epithelium
Pathology
Growth

Keywords

  • Bladder
  • Bladder progenitor cell
  • Directed differentiation
  • Embryonic mesenchyme
  • Embryonic stem cells
  • Endoderm
  • Urothelium

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Oottamasathien, S., Wang, Y. Q., Williams, K., Franco, O. E., Wills, M. L., Thomas, J. C., ... Matusik, R. J. (2007). Directed differentiation of embryonic stem cells into bladder tissue. Developmental Biology, 304(2), 556-566. https://doi.org/10.1016/j.ydbio.2007.01.010

Directed differentiation of embryonic stem cells into bladder tissue. / Oottamasathien, Siam; Wang, Yong Qing; Williams, Karin; Franco, Omar E.; Wills, Marcia L.; Thomas, John C.; Saba, Katrina; Sharif-Afshar, Ali Reza; Makari, John H.; Bhowmick, Neil A.; DeMarco, Romano T.; Hipkens, Susan; Magnuson, Mark; Brock, John W.; Hayward, Simon W.; Pope IV, John C.; Matusik, Robert J.

In: Developmental Biology, Vol. 304, No. 2, 15.04.2007, p. 556-566.

Research output: Contribution to journalArticle

Oottamasathien, S, Wang, YQ, Williams, K, Franco, OE, Wills, ML, Thomas, JC, Saba, K, Sharif-Afshar, AR, Makari, JH, Bhowmick, NA, DeMarco, RT, Hipkens, S, Magnuson, M, Brock, JW, Hayward, SW, Pope IV, JC & Matusik, RJ 2007, 'Directed differentiation of embryonic stem cells into bladder tissue', Developmental Biology, vol. 304, no. 2, pp. 556-566. https://doi.org/10.1016/j.ydbio.2007.01.010
Oottamasathien S, Wang YQ, Williams K, Franco OE, Wills ML, Thomas JC et al. Directed differentiation of embryonic stem cells into bladder tissue. Developmental Biology. 2007 Apr 15;304(2):556-566. https://doi.org/10.1016/j.ydbio.2007.01.010
Oottamasathien, Siam ; Wang, Yong Qing ; Williams, Karin ; Franco, Omar E. ; Wills, Marcia L. ; Thomas, John C. ; Saba, Katrina ; Sharif-Afshar, Ali Reza ; Makari, John H. ; Bhowmick, Neil A. ; DeMarco, Romano T. ; Hipkens, Susan ; Magnuson, Mark ; Brock, John W. ; Hayward, Simon W. ; Pope IV, John C. ; Matusik, Robert J. / Directed differentiation of embryonic stem cells into bladder tissue. In: Developmental Biology. 2007 ; Vol. 304, No. 2. pp. 556-566.
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