TY - JOUR
T1 - Adult corneal limbal epithelium
T2 - A model for studying neural potential of non-neural stem cells/progenitors
AU - Zhao, Xing
AU - Das, Ani V.
AU - Thoreson, Wallace B.
AU - James, Jackson
AU - Wattnem, Tami E.
AU - Rodriguez-Sierra, Jorge
AU - Ahmad, Iqbal
N1 - Funding Information:
This work was supported by NEI, the Foundation for Fighting Blindness, the Nebraska Research Initiative and Research to Prevent Blindness. We are grateful to Dr. James Zieske for antibody against α-enolase, and Ron McKay for ployclonal antibody against nestin and David Anderson for Mash1 antibody. Thanks are due to Eric Bryson for technical assistance with calcium imaging experiments and Bill Wassom for graphics.
PY - 2002
Y1 - 2002
N2 - Recent studies suggest that tissue-specific stem cells possess much wider potential for differentiation than previously thought and can, in some instances, even cross germ layer boundaries. However, information is lacking regarding the efficiency and the fidelity of their differentiation along heterologous lineages. To address these issues of transdifferentiation, we have analyzed the heterologous potential of stem cells within the same germ layer. We report the neural potential of cells isolated from the limbal epithelium of the adult cornea. Limbal epithelium, which, like the neuroepithelium, is ectodermally derived, participates in the regeneration of cornea throughout life. We have observed that limbal epithelial cells, when removed from their niche and cultured in the presence of mitogens, begin to express neural progenitor markers. Based on the self-renewal property, it is likely that the nestin-positive progenitors are derived from limbal stem cells rather than transit-amplifying (TA) cells that have limited proliferating potential. In differentiation conditions, a subset of these cells acquire neural morphology and express transcripts and proteins specific to neurons and glia, suggesting their differentiation along neural lineage. The acquisition of neural properties is regulated by BMP signaling. Neural differentiation of these cells is also observed upon heterotopic transplantation. Investigation of functional differentiation of cells by electrophysiological analysis reveals properties consistent with the presence of glia that are influenced by extracellular cues. However, similar analyses coupled with Ca2+ imaging suggest an incomplete differentiation of limbal epithelial-derived neural progenitors into neurons in the condition studied. Our study, therefore, draws attention toward the necessity for rigorous characterization of transdifferentiation and offers a model for characterizing neural potential of heterologous stem cells/progenitors.
AB - Recent studies suggest that tissue-specific stem cells possess much wider potential for differentiation than previously thought and can, in some instances, even cross germ layer boundaries. However, information is lacking regarding the efficiency and the fidelity of their differentiation along heterologous lineages. To address these issues of transdifferentiation, we have analyzed the heterologous potential of stem cells within the same germ layer. We report the neural potential of cells isolated from the limbal epithelium of the adult cornea. Limbal epithelium, which, like the neuroepithelium, is ectodermally derived, participates in the regeneration of cornea throughout life. We have observed that limbal epithelial cells, when removed from their niche and cultured in the presence of mitogens, begin to express neural progenitor markers. Based on the self-renewal property, it is likely that the nestin-positive progenitors are derived from limbal stem cells rather than transit-amplifying (TA) cells that have limited proliferating potential. In differentiation conditions, a subset of these cells acquire neural morphology and express transcripts and proteins specific to neurons and glia, suggesting their differentiation along neural lineage. The acquisition of neural properties is regulated by BMP signaling. Neural differentiation of these cells is also observed upon heterotopic transplantation. Investigation of functional differentiation of cells by electrophysiological analysis reveals properties consistent with the presence of glia that are influenced by extracellular cues. However, similar analyses coupled with Ca2+ imaging suggest an incomplete differentiation of limbal epithelial-derived neural progenitors into neurons in the condition studied. Our study, therefore, draws attention toward the necessity for rigorous characterization of transdifferentiation and offers a model for characterizing neural potential of heterologous stem cells/progenitors.
KW - BMP signaling
KW - Limbal epithelium
KW - Neural stem cells
KW - Progenitors
KW - Reprogramming
KW - Transdifferentiation
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UR - http://www.scopus.com/inward/citedby.url?scp=0036402525&partnerID=8YFLogxK
U2 - 10.1016/S0012-1606(02)90793-1
DO - 10.1016/S0012-1606(02)90793-1
M3 - Article
C2 - 12376106
AN - SCOPUS:0036402525
SN - 0012-1606
VL - 250
SP - 317
EP - 331
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -