p53 switches off pluripotency on differentiation

Lin, Tongxiang; Lin, Yi

doi:10.1186/s13287-017-0498-1

Cited by 37 publications

(43 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study also demonstrated that ELPC recovered the transcriptional function of mutant p53 27 . Recent studies have confirmed that p53 regulates the differentiation of embryonic stem cells and induces pluripotent stem cells in response to genomic damage, similar to our results 28,29 .…”

Section: Discussionsupporting

confidence: 92%

Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9

Lee

Park

et al. 2020

Exp Mol Med

View full text Add to dashboard Cite

Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into functional chondrocytes, the currently available methods cannot induce stem cells to undergo differentiation into chondrocyte-like cells without inducing characteristics of hypertrophic chondrocytes, which finally lead to cartilage disintegration and calcification. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. This study focused on differentiating adipose-derived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 as a key factor in cartilage development and then explored its ability to treat OA. We selected ellipticine (ELPC), which induces chondrocyte differentiation of ASCs, using a GFP-Sox9 promoter vector screening system. An in vivo study was performed to confirm the recovery rate of cartilage regeneration with ASC differentiation into chondrocytes by ELPC in a collagenase-induced animal model of OA. Taken together, these data indicate that ellipticine induces ASCs to differentiate into mature chondrocytes without hypertrophic chondrocytes in vitro and in vivo, thus overcoming a problem encountered in previous studies. These results indicate that ELPC is a novel chondrocyte differentiationinducing drug that shows potential as a cell therapy for OA.

show abstract

Section: Discussionsupporting

confidence: 92%

Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9

Lee

Park

et al. 2020

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…gene sets involved in intestinal epithelial cell differentiationrelated genes were downregulated in both mutated TP53 cells, indicating that TP53WT might promote the differentiation of cancer cells. In normal cells, TP53WT has been suggested as a contributor to the process of switching off pluripotency upon differentiation (25), because TP53WT in the colon cancer cell might contribute to the transition of cancer stem cells to differentiated cancer cells. In Fig.…”

Section: Discussionmentioning

confidence: 99%

TP53 Mutation by CRISPR System Enhances the Malignant Potential of Colon Cancer

Watanabe

Tsuchiya

Nishimura

et al. 2019

Molecular Cancer Research

View full text Add to dashboard Cite

Tumor protein p53 (TP53) mutation is a well-known occurrence at the late phase of carcinogenesis during the adenoma-carcinoma sequence of a sporadic colon cancer. Although numerous reports about clinical information of the patients with colon cancer have suggested that TP53 mutation might be related to various types of malignant potential, the direct effects of this mutation on the malignant potential of colon cancer remain unknown. Notably, no previous report has described a relationship between TP53 mutation and cancer stemness. We therefore aimed to assess the function of a TP53 mutant induced by the CRISPR-Cas9 system in colon cancer cells. In this study, two TP53 mutations, corresponding to exon 3 (TP53E3) and 10 (TP53E10), were generated in LS174T cells derived from a wild-type TP53 human colon cancer via a lentiviral CRISPR-Cas9 system. The loss of function of TP53 resulting from both mutations manifested as resistance to Nutlin3a-induced apoptosis and the downregulation of target genes of TP53. TP53 mutants exhibited an enhanced malignant potential, characterized by accelerated cell growth, invasiveness, chemoresistance, and cancer stemness. Interestingly, TP53E10 but not TP53E3 cells exhibited aberrant transcriptional activity of regenerating family member 1-a (REG1A) and expression of REG1A, resulting in the acquisition of enhanced malignant potential. In conclusion, we demonstrated for the first time that TP53 genomic mutation into human colon cancer cells affects the malignant potential. Implications: These findings suggest that both a loss of function and an aberrant gain of function of TP53 might promote high malignant potentials at the late phase of carcinogenesis in colon cancer.

show abstract

“…p53 is highly expressed in mouse ESCs in the cytoplasm under basal conditions (Aladjem et al 1998, Solozobova et al 2009 and functions to maintain genome stability in ESCs by inducing apoptosis upon DNA damage and differentiation (He et al 2016). p53 reduces reprogramming efficiency of somatic cells to pluripotent stem cells and its inhibition enhances reprogramming efficiency (reviewed in Lin & Lin 2017).…”

Section: Comparative Analysis Of Pluripotency Among Primates and Mousementioning

confidence: 99%

The quest for pluripotency: a comparative analysis across mammalian species

et al. 2019

View full text Add to dashboard Cite

Pluripotency is the developmental potential of a cell to give rise to all the cells in the three embryonic germ layers, including germline cells. Pluripotent stem cells (PSCs) can be embryonic, germ cell or somatic cell in origin and can adopt alternative states of pluripotency: naïve or primed. Although several reports have described the differentiation of PSCs to extra-embryonic lineages, such as primitive endoderm and trophectoderm, this is still debated among scientists in the field. In this review, we integrate the recent findings on pluripotency among mammals, alternative states of pluripotency, signalling pathways associated with maintaining pluripotency and the nature of PSCs derived from various mammals. PSCs from humans and mouse have been the most extensively studied. In other mammalian species, more research is required for understanding the optimum in vitro conditions required for either achieving pluripotency or preservation of distinct pluripotent states. A comparative high-throughput analysis of PSCs of genes expressed in naïve or primed states of humans, nonhuman primates (NHP) and rodents, based on publicly available datasets revealed the probable prominence of seven signalling pathways common among these species, irrespective of the states of pluripotency. We conclude by highlighting some of the unresolved questions and future directions of research on pluripotency in mammals.

show abstract

p53 switches off pluripotency on differentiation

Cited by 37 publications

References 49 publications

Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9

Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9

TP53 Mutation by CRISPR System Enhances the Malignant Potential of Colon Cancer

The quest for pluripotency: a comparative analysis across mammalian species

Contact Info

Product

Resources

About