Rebuilding Pluripotency from Primordial Germ Cells
File(s)Rebuilding pluripotency from primordial germ cells.pdf (2.41 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Mammalian primordial germ cells (PGCs) are unipotent progenitors of the gametes. Nonetheless, they can give rise directly to pluripotent stem cells in vitro or during teratocarcinogenesis. This conversion is inconsistent, however, and has been difficult to study. Here, we delineate requirements for efficient resetting of pluripotency in culture. We demonstrate that in defined conditions, routinely 20% of PGCs become EG cells. Conversion can occur from the earliest specified PGCs. The entire process can be tracked from single cells. It is driven by leukemia inhibitory factor (LIF) and the downstream transcription factor STAT3. In contrast, LIF signaling is not required during germ cell ontogeny. We surmise that ectopic LIF/STAT3 stimulation reconstructs latent pluripotency and self-renewal. Notably, STAT3 targets are significantly upregulated in germ cell tumors, suggesting that dysregulation of this pathway may underlie teratocarcinogenesis. These findings demonstrate that EG cell formation is a robust experimental system for exploring mechanisms involved in reprogramming and cancer.
Date Issued
2013-06-04
Date Acceptance
2013-03-23
Citation
STEM CELL REPORTS, 2013, 1 (1), pp.66-78
ISSN
2213-6711
Publisher
CELL PRESS
Start Page
66
End Page
78
Journal / Book Title
STEM CELL REPORTS
Volume
1
Issue
1
Copyright Statement
© 2013 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which
permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000336632000009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell & Tissue Engineering
Cell Biology
EMBRYONIC STEM-CELLS
GROUND-STATE PLURIPOTENCY
SELF-RENEWAL
GROWTH-FACTOR
IN-VITRO
MOUSE
MICE
DERIVATION
LINEAGE
CULTURE
Publication Status
Published
Date Publish Online
2013-06-04