Compromised Chondrocyte Differentiation Capacity in TERC Knockout Mouse Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

被引：5

作者：

Chang, Wei-Fang ^{[1
]}

Wu, Yun-Hsin ^{[1
]}

Xu, Jie ^{[2
]}

Sung, Li-Ying ^{[1
,3
,4
,5
]}

机构：

[1] Natl Taiwan Univ, Inst Biotechnol, Taipei 106, Taiwan

[2] Univ Michigan, Med Ctr, Ctr Adv Models Translat Sci & Therapeut, Ann Arbor, MI 48109 USA

[3] Acad Sinica, Agr Biotechnol Res Ctr, Taipei 115, Taiwan

[4] Natl Taiwan Univ, Anim Resource Ctr, Taipei 106, Taiwan

[5] Natl Taiwan Univ, Ctr Biotechnol, Taipei 106, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 05期

关键词：

telomeres; telomerase; embryonic stem cells; mesoderm; mouse; BONE-MARROW FAILURE; TELOMERE LENGTH; ELONGATION; WERNER;

D O I：

10.3390/ijms20051236

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mammalian telomere lengths are primarily regulated by telomerase, consisting of a reverse transcriptase protein (TERT) and an RNA subunit (TERC). We previously reported the generation of mouse Terc(+/-) and Terc(-/-) embryonic stem cells (ntESCs) by somatic cell nuclear transfer. In the present work, we investigated the germ layer development competence of Terc(-/-), Terc(+/-) and wild-type (Terc(+/+)) ntESCs. The telomere lengths are longest in wild-type but shortest in Terc(-/-) ntESCs, and correlate reversely with the population doubling time. Interestingly, while in vitro embryoid body (EB) differentiation assay reveals EB size difference among ntESCs of different genotypes, the more stringent in vivo teratoma assay demonstrates that Terc(-/-) ntESCs are severely defective in differentiating into the mesodermal lineage cartilage. Consistently, in a directed in vitro chondrocyte differentiation assay, the Terc(-/-) cells failed in forming Collagen II expressing cells. These findings underscore the significance in maintaining proper telomere lengths in stem cells and their derivatives for regenerative medicine.

引用

页数：12

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