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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 313 - 321 (9page)
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Background Under hypoxia, mouse embryonic stem cells (mESCs) lose the ability to self-renew and begin to differentiate through down-regulation of LIFR-STAT3 pathway via hypoxia-inducible factor-1α (HIF-1α). However, it remains largely unknown what kinds of factors are involved in hypoxia-induced differentiation of mESCs. Purpose This study aims to identify the differentially expressed genes (DEGs) in early differentiation of mESCs under hypoxia. Methods Here we utilized a Genefishing techniqueTM to discover the new DEGs during hypoxia-induced early differentiation in CCE mESCs. Next, we investigated the role of DEGs using morphological observation, alkaline phosphatase (ALP) assay, STAT3 activation analysis, and biomarkers analysis for stemness. Results We detected 19 DEGs under hypoxia and performed cloning with sequencing in six genes. We confirmed the expression patterns of five DEGs including H2afz and GOT1 by realtime PCR assay. Among them, H2afz was significantly decreased under hypoxia, depending on HIF-1α. H2afz-overexpressing CCE mESCs maintained their ALP activity and stem cell markers (Nanog and Rex1), even in hypoxic condition. On the other hand, the early differentiation markers such as FGF5 and STAT5a, which had been increased in hypoxic conditions, were reduced by H2afz overexpression. Conclusion We discovered that H2afz could be a new target gene that functions in hypoxia-induced differentiation in mESCs and have revealed that it is involved in maintaining the pluripotency of mESCs in the early stages of differentiation. These findings will provide insights into mechanisms of hypoxia-mediated differentiation of mESCs during early development.
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참고문헌 (31)
참고문헌 신청
Bost F / 2002 / Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage / Biochem J 361:621~627
Coleman-Derr D / 2012 / Deposition of histone variant H2A. Z within gene bodies regulates responsive genes / PLoS Genet 8:e1002988
Du Z / 2001 / Identifcation of putative downstream genes of Oct-4 by suppression-subtractive hybridization / Biochem Biophys Res Commun 282:701~706
Du KL / 2004 / Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell diferentiation from undifferentiated embryonic stem cells / J Biol Chem 279:17578~17586
Ernst M / 1999 / The carboxyl-terminal domains of gp130-related cytokine receptors are necessary for suppressing embryonic stem cell diferentiation. Involvement of STAT3 / J Biol Chem 274:9729~9737
Coleman-Derr D / 2012 / Deposition of histone variant H2A. Z within gene bodies regulates responsive genes / PLoS Genet 8:e1002988
Du Z / 2001 / Identifcation of putative downstream genes of Oct-4 by suppression-subtractive hybridization / Biochem Biophys Res Commun 282:701~706
Du KL / 2004 / Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell diferentiation from undifferentiated embryonic stem cells / J Biol Chem 279:17578~17586
Ernst M / 1999 / The carboxyl-terminal domains of gp130-related cytokine receptors are necessary for suppressing embryonic stem cell diferentiation. Involvement of STAT3 / J Biol Chem 274:9729~9737
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