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Generation of Human Primordial Germ Cell-like Cells at the Surface of Embryoid Bodies from Primed-pluripotency Induced Pluripotent Stem Cells
Published on: January 11, 2019
Rebuilding pluripotency from primordial germ cells
Harry G Leitch1, Jennifer Nichols, Peter Humphreys
1Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK ; Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Stem Cell Reports
|September 21, 2013
Summary
Mammalian primordial germ cells (PGCs) can efficiently reset to pluripotent stem cells in culture. This conversion is driven by leukemia inhibitory factor (LIF) and STAT3 signaling, offering insights into reprogramming and cancer.
Area of Science:
- Stem cell biology
- Developmental biology
- Cancer research
Background:
- Mammalian primordial germ cells (PGCs) are gamete progenitors but can dedifferentiate into pluripotent stem cells in vitro and in vivo.
- This conversion process has been inconsistent and challenging to study.
Purpose of the Study:
- To define the requirements for efficient reprogramming of PGCs into pluripotent cells in culture.
- To investigate the role of leukemia inhibitory factor (LIF) and STAT3 signaling in this process.
Main Methods:
- Culturing PGCs under defined conditions.
- Tracking the conversion of single PGCs to embryonic germ (EG) cells.
- Analyzing the role of LIF and STAT3 signaling pathways.
Main Results:
- Defined conditions enable routine conversion of ~20% of PGCs to EG cells, from the earliest stages.
- The entire reprogramming process is driven by LIF and STAT3 signaling.
- LIF signaling is not essential for normal germ cell development but is crucial for in vitro pluripotency induction.
Conclusions:
- Ectopic LIF/STAT3 signaling can reactivate latent pluripotency and self-renewal in PGCs.
- Upregulation of STAT3 targets in germ cell tumors suggests its dysregulation may drive teratocarcinogenesis.
- EG cell formation provides a robust model for studying reprogramming and cancer mechanisms.
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