Rebuilding Pluripotency from Primordial Germ Cells

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...

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Main Authors:	Leitch, Harry G., Nichols, Jennifer, Humphreys, Peter, Mulas, Carla, Martello, Graziano, Lee, Caroline, Jones, Ken, Surani, M. Azim, Smith, Austin
Format:	Online
Language:	English
Published:	Elsevier 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757743/

id	pubmed-3757743
recordtype	oai_dc
spelling	pubmed-37577432013-09-17 Rebuilding Pluripotency from Primordial Germ Cells Leitch, Harry G. Nichols, Jennifer Humphreys, Peter Mulas, Carla Martello, Graziano Lee, Caroline Jones, Ken Surani, M. Azim Smith, Austin Article 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. Elsevier 2013-06-04 /pmc/articles/PMC3757743/ /pubmed/24052943 http://dx.doi.org/10.1016/j.stemcr.2013.03.004 Text en © 2013 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Leitch, Harry G. Nichols, Jennifer Humphreys, Peter Mulas, Carla Martello, Graziano Lee, Caroline Jones, Ken Surani, M. Azim Smith, Austin
spellingShingle	Leitch, Harry G. Nichols, Jennifer Humphreys, Peter Mulas, Carla Martello, Graziano Lee, Caroline Jones, Ken Surani, M. Azim Smith, Austin Rebuilding Pluripotency from Primordial Germ Cells
author_facet	Leitch, Harry G. Nichols, Jennifer Humphreys, Peter Mulas, Carla Martello, Graziano Lee, Caroline Jones, Ken Surani, M. Azim Smith, Austin
author_sort	Leitch, Harry G.
title	Rebuilding Pluripotency from Primordial Germ Cells
title_short	Rebuilding Pluripotency from Primordial Germ Cells
title_full	Rebuilding Pluripotency from Primordial Germ Cells
title_fullStr	Rebuilding Pluripotency from Primordial Germ Cells
title_full_unstemmed	Rebuilding Pluripotency from Primordial Germ Cells
title_sort	rebuilding pluripotency from primordial germ cells
description	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.
publisher	Elsevier
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757743/
_version_	1612007080862941184

Rebuilding Pluripotency from Primordial Germ Cells

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