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Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming
Christiana Hadjimichael1, Konstantina Chanoumidou2, Christoforos Nikolaou3
1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece.
Insights
Promyelocytic leukemia protein (PML) is vital for maintaining embryonic stem cell (ESC) pluripotency and self-renewal. PML also influences cell fate during differentiation and enhances somatic cell reprogramming.
Area of Science:
- Stem cell biology
- Molecular and cell biology
- Developmental biology
Background:
- Promyelocytic leukemia protein (PML) is a key component of nuclear bodies and regulates diverse cellular processes.
- The role of PML in embryonic stem cells (ESCs) and their pluripotency remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of PML in maintaining ESC self-renewal and pluripotency.
- To elucidate PML's role in ESC differentiation and somatic cell reprogramming.
Main Methods:
- Gain- and loss-of-function studies in ESCs.
- Transcriptomic analysis.
- Embryoid body differentiation assays.
- Somatic cell reprogramming experiments.
Main Results:
- PML deficiency in ESCs alters morphology, metabolism, and growth, shifting them towards a primed pluripotent state.
- PML regulates cell-cycle progression and sustains pluripotency factors in ESCs.
- PML influences mesoderm and endoderm fate decisions during embryoid body differentiation by controlling Tbx3 expression.
- PML loss impairs somatic cell reprogramming by inhibiting the transforming growth factor β pathway.
Conclusions:
- PML is integral to the regulatory network governing ESC naive pluripotency.
- PML plays a critical role in somatic cell reprogramming to induced pluripotent stem cells.
- PML is a significant regulator of cell-cycle progression, pluripotency, differentiation, and reprogramming.
Abstract:
Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. During differentiation of embryoid bodies, PML influences cell-fate decisions between mesoderm and endoderm by controlling the expression of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced pluripotent stem cells by inhibiting the transforming growth factor β pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC naive pluripotency and somatic cell reprogramming.