Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation

Ri ichiro Kohno, Yasuhiro Ikeda, Yoshikazu Yonemitsu, Toshio Hisatomi, Masahiro Yamaguchi, Masanori Miyazaki, Hiroko Takeshita, Tatsuro Ishibashi, Katsuo Sueishi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/μl). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations.

Original languageEnglish
Pages (from-to)54-70
Number of pages17
JournalBrain Research
Volume1093
Issue number1
DOIs
Publication statusPublished - Jun 6 2006

Fingerprint

Ciliary Body
Nestin
Epithelial Cells
Central Nervous System
Epithelium
Cell Proliferation
Growth Inhibitors
Neural Stem Cells
Intermediate Filaments
Growth
Cell Differentiation
Cultured Cells
Cell Cycle
Stem Cells
Population

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation. / Kohno, Ri ichiro; Ikeda, Yasuhiro; Yonemitsu, Yoshikazu; Hisatomi, Toshio; Yamaguchi, Masahiro; Miyazaki, Masanori; Takeshita, Hiroko; Ishibashi, Tatsuro; Sueishi, Katsuo.

In: Brain Research, Vol. 1093, No. 1, 06.06.2006, p. 54-70.

Research output: Contribution to journalArticle

Kohno, Ri ichiro ; Ikeda, Yasuhiro ; Yonemitsu, Yoshikazu ; Hisatomi, Toshio ; Yamaguchi, Masahiro ; Miyazaki, Masanori ; Takeshita, Hiroko ; Ishibashi, Tatsuro ; Sueishi, Katsuo. / Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation. In: Brain Research. 2006 ; Vol. 1093, No. 1. pp. 54-70.
@article{8158fbced1914c518666e338f22074f7,
title = "Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation",
abstract = "It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/μl). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations.",
author = "Kohno, {Ri ichiro} and Yasuhiro Ikeda and Yoshikazu Yonemitsu and Toshio Hisatomi and Masahiro Yamaguchi and Masanori Miyazaki and Hiroko Takeshita and Tatsuro Ishibashi and Katsuo Sueishi",
year = "2006",
month = "6",
day = "6",
doi = "10.1016/j.brainres.2006.03.093",
language = "English",
volume = "1093",
pages = "54--70",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation

AU - Kohno, Ri ichiro

AU - Ikeda, Yasuhiro

AU - Yonemitsu, Yoshikazu

AU - Hisatomi, Toshio

AU - Yamaguchi, Masahiro

AU - Miyazaki, Masanori

AU - Takeshita, Hiroko

AU - Ishibashi, Tatsuro

AU - Sueishi, Katsuo

PY - 2006/6/6

Y1 - 2006/6/6

N2 - It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/μl). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations.

AB - It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/μl). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations.

UR - http://www.scopus.com/inward/record.url?scp=33745430746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745430746&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2006.03.093

DO - 10.1016/j.brainres.2006.03.093

M3 - Article

VL - 1093

SP - 54

EP - 70

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -