Stemness factor Sall4 is required for DNA damage response in embryonic stem cells

Xiong, Jie; Todorova, Dilyana; Su, Ning-Yuan; Kim, Jin Chul; Lee, Pei-Jen; Shen, Zhouxin; Briggs, Steven P.; Xu, Yiming

doi:10.1083/jcb.201408106

Cited by 51 publications

(28 citation statements)

References 26 publications

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“…Mouse and human pluripotent SCs exhibit important differences that should be considered in any analysis. The majority of previous studies have been conducted with mouse ESCs (mESCs) (19–21). However, these results cannot be directly applied to human cells.…”

Section: Discussionmentioning

confidence: 99%

“…Although mESCs and hESCs are well-understood, little is known about miPSCs, and information about hiPSCs is limited. mESCs have increased genetic stability compared with differentiated cells because, in response to DSBs, the recruitment of the stemness factor spalt like transcription factor 4 is required to activate the critical ataxia telaniectasia mutated (ATM)-dependent cellular pathway (19). In somatic cells, cyclin-dependent kinase 2 ( CDK2 ), the major regulator of the G 1 /S transition, is impaired by cell division cycle 25A ( CDC25A ) phosphatase, which initiates G 1 checkpoint.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

Suchorska

Augustyniak

Łukjanow

2017

Molecular Medicine Reports

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Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment-associated purposes. Therefore, the aim of the present study was to examine and compare early IR-induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non-homologous end-joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC-based clinical protocols.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

Suchorska

Augustyniak

Łukjanow

2017

Molecular Medicine Reports

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“…Furthermore, Sall4 interacts with Oct4, Nanog, or Sox2 to maintain “stemness” of ESCs. There are further reports of SALL4 interaction with TBX5 in cardiac tissues 18 , with PLZF in spermatogonial progenitors in postnatal testes 117 , and with Rad50 to stabilize the Mre11–Rad50–Nbs1 complex during the DNA damage repair process 118 . We have detailed some of these interactions below.…”

Section: Molecular Dissection Of Sall4 Functions In Cellsmentioning

confidence: 99%

“…Identified by mass-spec and confirmed by co-IP, Sall4 interacts with Rad50 and stabilizes the Mre11–Rad50–Nbs1 complex for the efficient recruitment and activation of ATM. Further, Sall4 interacts with Baf60a, a member of the SWI/SNF (switch/sucrose nonfermentable) ATP-dependent chromatin-remodeling complex, which may be responsible for recruiting Sall4 to the site of DNA DSB 118 .…”

Section: Molecular Dissection Of Sall4 Functions In Cellsmentioning

confidence: 99%

SALL4, the missing link between stem cells, development and cancer

Tatetsu

Kong

Gao

et al. 2016

Gene

109

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There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment. This is an exciting cancer-targeting model. The major hurdle to test this model is to identify the key factors/pathway(s) within ESCs that are responsible for the cancer phenotype. SALL4 is one of few genes that can establish this link. The first publication of SALL4 is on its mutation in a human inherited disorder with multiple developmental defects. Since then, over 300 papers have been published on various aspects of this gene in stem cells, development, and cancers. This review aims to summarize our current knowledge of SALL4, including a SALL4-based approach to classify and target cancers. Many questions about this important gene still remain unanswered, specifically, on how this gene regulates cell fates at a molecular level. Understanding SALL4’s molecular functions will allow development of specific targeted approaches in the future.

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“…4, 5 In addition, SALL4 is critical for DNA damage response in embryonic stem cells. 6 SALL4 expression gradually decreases during development and is even absent in most adult tissues. However, there is increasing evidence showing that SALL4 expression is re-stored in cancer.…”

Section: Introductionmentioning

confidence: 99%

SALL4 promotes gastric cancer progression through activating CD44 expression

Yuan

Zhang

et al. 2016

Oncogenesis

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The stem cell factor SALL4 (Sal-like protein 4) plays important roles in the development and progression of cancer. SALL4 is critically involved in tumour growth, metastasis and therapy resistance. However, the underlying mechanisms responsible for the oncogenic roles of SALL4 have not been well characterized. In this study, we demonstrated that SALL4 knockdown by short hairpin RNA greatly inhibited the proliferation, migration and invasion of gastric cancer cells. We further confirmed the inhibitory effects of SALL4 knockdown on gastric cancer cells by using a tetracycline-inducible system. Mechanistically, SALL4 knockdown downregulated the expression of CD44. The results of luciferase assay and chromatin immunoprecipitation study showed that SALL4 bound to CD44 promoter region and transcriptionally activated CD44. The results of rescue study revealed that CD44 overexpression antagonized SALL4 knockdown-mediated inhibition of gastric cancer cell proliferation, migration, and invasion in vitro and gastric cancer growth in vivo. Collectively, our findings indicate that SALL4 promotes gastric cancer progression through directly activating CD44 expression, which suggests a novel mechanism for the oncogenic roles of SALL4 in gastric cancer and represents a new target for gastric cancer therapy.

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Stemness factor Sall4 is required for DNA damage response in embryonic stem cells

Abstract: Sall4 is important for the activation of ATM-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse embryonic stem cells and confers resistance to DSB-induced cytotoxicity.

Cited by 51 publications

References 26 publications

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

SALL4, the missing link between stem cells, development and cancer

SALL4 promotes gastric cancer progression through activating CD44 expression

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