Rebuilding Pluripotency from Primordial Germ Cells

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Title: Rebuilding Pluripotency from Primordial Germ Cells
Authors: Leitch, HG
Nichols, J
Humphreys, P
Mulas, C
Martello, G
Lee, C
Jones, K
Surani, MA
Smith, A
Item 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.
Issue Date: 4-Jun-2013
Date of Acceptance: 23-Mar-2013
URI: http://hdl.handle.net/10044/1/62062
DOI: https://dx.doi.org/10.1016/j.stemcr.2013.03.004
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.
Keywords: 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
Animals
Cell Differentiation
Cell Lineage
Embryonic Stem Cells
Germ Cells
Leukemia Inhibitory Factor
Mice
Neoplasms, Germ Cell and Embryonal
Pluripotent Stem Cells
STAT3 Transcription Factor
Up-Regulation
Germ Cells
Pluripotent Stem Cells
Animals
Mice
Neoplasms, Germ Cell and Embryonal
Cell Differentiation
Up-Regulation
Cell Lineage
STAT3 Transcription Factor
Leukemia Inhibitory Factor
Embryonic Stem Cells
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
Online Publication Date: 2013-06-04
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine



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