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Study Challenges Long-held Assumption of Gene Expression in Embryonic Stem Cells

July 3, 2013

CAMBRIDGE, Mass. – Whitehead Institute researchers have determined that the transcription factor Nanog, which plays a critical role in the self-renewal of embryonic stem cells, is expressed in a manner similar to other pluripotency markers. This finding contradicts the field’s presumptions about this important gene and its role in the differentiation of embryonic stem cells.

A large body of research has reported that Nanog is allelically regulated—that is, only one copy of the gene is expressed at any given time—and fluctuations in its expression are responsible for the differences seen in individual embryonic stem (ES) cells’ predilection to differentiate into more specialized cells. These studies relied on cells that had a genetic marker or reporter inserted in the DNA upstream of the Nanog gene. This latest research, published in this week’s edition of the journal Cell Stem Cell, suggests that results from studies based on this approach could be called into question.

To quantify the variations in Nanog expression, Dina Faddah, a graduate student in the lab of Whitehead Institute Founding Member Rudolf Jaenisch, looked at hundreds of individual mouse ES cells with reporters inserted immediately downstream of the Nanog gene. One Nanog allele had a green reporter, while the other had a red reporter, allowing Faddah to determine which of the two alleles was being expressed.

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