Jiaqi Yang
Chinese Academy of Sciences
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Publication
Featured researches published by Jiaqi Yang.
Nature Genetics | 2013
Jiekai Chen; He Liu; Jing Liu; Jing Qi; Bei Wei; Jiaqi Yang; Hanquan Liang; You Chen; Jing Chen; Yaran Wu; Lin Guo; Jieying Zhu; Xiangjie Zhao; Tianran Peng; Yixin Zhang; Shen Chen; Xuejia Li; Dongwei Li; Tao Wang; Duanqing Pei
The induction of pluripotent stem cells (iPSCs) by defined factors is poorly understood stepwise. Here, we show that histone H3 lysine 9 (H3K9) methylation is the primary epigenetic determinant for the intermediate pre-iPSC state, and its removal leads to fully reprogrammed iPSCs. We generated a panel of stable pre-iPSCs that exhibit pluripotent properties but do not activate the core pluripotency network, although they remain sensitive to vitamin C for conversion into iPSCs. Bone morphogenetic proteins (BMPs) were subsequently identified in serum as critical signaling molecules in arresting reprogramming at the pre-iPSC state. Mechanistically, we identified H3K9 methyltransferases as downstream targets of BMPs and showed that they function with their corresponding demethylases as the on/off switch for the pre-iPSC fate by regulating H3K9 methylation status at the core pluripotency loci. Our results not only establish pre-iPSCs as an epigenetically stable signpost along the reprogramming road map, but they also provide mechanistic insights into the epigenetic reprogramming of cell fate.
Nature Genetics | 2013
Jiekai Chen; Lin Guo; Lei Zhang; Haoyu Wu; Jiaqi Yang; He Liu; Xiaoshan Wang; Xiao Hu; Tian-Peng Gu; Zhiwei Zhou; Jing Liu; Jiadong Liu; Hongling Wu; Shi-Qing Mao; Kunlun Mo; Yingying Li; Keyu Lai; Jing Qi; Hongjie Yao; Guangjin Pan; Guoliang Xu; Duanqing Pei
Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases. TET hydroxylases are also dioxygenases implicated in active DNA demethylation. Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C. TET1 deficiency enhances reprogramming, and its overexpression impairs reprogramming in the context of vitamin C by modulating the obligatory mesenchymal-to-epithelial transition (MET). In the absence of vitamin C, TET1 promotes somatic cell reprogramming independent of MET. Consistently, TET1 regulates 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C–dependent fashion. Our findings suggest that vitamin C has a vital role in determining the biological outcome of TET1 function at the cellular level. Given its benefit to human health, vitamin C should be investigated further for its role in epigenetic regulation.
Cell Research | 2011
Jiekai Chen; Jing Liu; Jiaqi Yang; You Chen; Jing Chen; Su Ni; Hong Song; Lingwen Zeng; Ke Ding; Duanqing Pei
Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to ∼1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.
Cell Research | 2011
Jiekai Chen; Jing Liu; You Chen; Jiaqi Yang; Jing Chen; He Liu; Xiangjie Zhao; Kunlun Mo; Hong Song; Lin Guo; Shilong Chu; Deping Wang; Ke Ding; Duanqing Pei
The ectopic expression of several transcription factors can restore embryonic cell fate to cultured somatic cells and generate induced pluripotent stem cells (iPSCs), revealing a previously unknown pathway to pluripotency. However, this technology is currently limited by low efficiency, slow kinetics and multi-factorial requirement. Here we show that reprogramming can be improved and dramatically accelerated by optimizing culture conditions. First, we developed an optimized defined medium, iCD1, which allows Oct4/Sox2/Klf4 (OSK)-mediated reprogramming to achieve ultra-high efficiency (∼10% at day 8). We also found that this optimized condition renders both Sox2 and Klf4 dispensable, although the elimination of these two factors leads to lower efficiency and slower kinetics. Our studies define a shortened route, both in timing and factor requirement, toward pluripotency. This new paradigm not only provides a rationale to further improve iPSC generation but also simplifies the conceptual understanding of reprogramming by defined factors.
Journal of Biological Chemistry | 2010
Jiekai Chen; Jing Liu; Qingkai Han; Dajiang Qin; Jianyong Xu; You Chen; Jiaqi Yang; Hong Song; Dongshan Yang; Meixiu Peng; Wenzhi He; Ronghui Li; Hao Wang; Yi Gan; Ke Ding; Lingwen Zeng; Liangxue Lai; Miguel A. Esteban; Duanqing Pei
Generation of induced pluripotent stem cells from somatic cells using defined factors has potential relevant applications in regenerative medicine and biology. However, this promising technology remains inefficient and time consuming. We have devised a serum free culture medium termed iSF1 that facilitates the generation of mouse induced pluripotent stem cells. This optimization of the culture medium is sensitive to the presence of Myc in the reprogramming factors. Moreover, we could reprogram meningeal cells using only two factors Oct4/Klf4. Therefore, iSF1 represents a basal medium that may be used for mechanistic studies and testing new reprogramming approaches.
Nature Cell Biology | 2015
Jing Liu; Qingkai Han; Tianran Peng; Meixiu Peng; Bei Wei; Dongwei Li; Xiaoshan Wang; Shengyong Yu; Jiaqi Yang; Shangtao Cao; Kaimeng Huang; Andrew Paul Hutchins; He Liu; Junqi Kuang; Zhiwei Zhou; Jing Chen; Haoyu Wu; Lin Guo; Yongqiang Chen; You Chen; Xuejia Li; Hongling Wu; Baojian Liao; Wei He; Hong Song; Hongjie Yao; Guangjin Pan; Jiekai Chen; Duanqing Pei
Oncogenic transcription factors are known to mediate the conversion of somatic cells to tumour or induced pluripotent stem cells (iPSCs). Here we report c-Jun as a barrier for iPSC formation. c-Jun is expressed by and required for the proliferation of mouse embryonic fibroblasts (MEFs), but not mouse embryonic stem cells (mESCs). Consistently, c-Jun is induced during mESC differentiation, drives mESCs towards the endoderm lineage and completely blocks the generation of iPSCs from MEFs. Mechanistically, c-Jun activates mesenchymal-related genes, broadly suppresses the pluripotent ones, and derails the obligatory mesenchymal to epithelial transition during reprogramming. Furthermore, inhibition of c-Jun by shRNA, dominant-negative c-Jun or Jdp2 enhances reprogramming and replaces Oct4 among the Yamanaka factors. Finally, Jdp2 anchors 5 non-Yamanaka factors (Id1, Jhdm1b, Lrh1, Sall4 and Glis1) to reprogram MEFs into iPSCs. Our studies reveal c-Jun as a guardian of somatic cell fate and its suppression opens the gate to pluripotency.
bioRxiv | 2017
Lin Guo; Xiaoshan Wang; Mingwei Gao; Lihui Lin; Junqi Kuang; Yuanbang Mai; Fang Wu; He Liu; Jiaqi Yang; Shilong Chu; Hong Song; Yujian Liu; Jiadong Liu; Jinyong Wang; Guangjin Pan; Andrew Paul Hutchins; Jing Liu; Jiekai Chen; Duanqing Pei
The Yamanaka factors convert mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through a highly heterogeneous process. Here we profile single cells undergoing an optimized 7-day reprogramming process and show that cells start reprogramming relatively in sync, but diverge into two branches around day 2. The first branch of cells expressing Cd34/Fxyd5/Psca become nonpluripotent. The second one contains cells that are first Oct4+, then Dppa5a+ and pluripotent. We show that IFN-γ blocks this late transition. Our results reveal the heterogeneous nature of somatic cell reprogramming, identify Dppa5a as a marker for pluripotent and innate immunity as a potential barrier for reprogramming. One Sentence Summary Single cell RNA sequencing reveals a continuum of cell fates from somatic to pluripotent and Dppa5a as a marker for chimera-competent iPSCs.
Nature Cell Biology | 2015
Jing Liu; Qingkai Han; Tianran Peng; Meixiu Peng; Bei Wei; Dongwei Li; Xiaoshan Wang; Shengyong Yu; Jiaqi Yang; Shangtao Cao; Kaimeng Huang; Andrew P. Hutchins; He Liu; Junqi Kuang; Zhiwei Zhou; Jiekai Chen; Hongling Wu; Lin Guo; Yongqiang Chen; Xuejia Li; Baojian Liao; He W; Hong Song; Hongjie Yao; Guangjin Pan; Duanqing Pei
Nat. Cell Biol. 17, 856–867 (2015); published online 22 June 2015; corrected after print 10 August 2015 In the version of this Article originally published, panels from Fig. 8e were mistakenly reproduced as Fig. 6g. The correct panels for Fig. 6g (KS/Jdp2-iPSC) are shown here and have been amended in all online versions of the Article.
Journal of Applied Physics | 2009
Wen Ren; Jiaqi Yang; Yuwei Zhang; D. Li; Z. H. Wang; X. G. Zhao; Z. D. Zhang
Single-phase epitaxial La0.47Ce0.20Ca0.33MnO3−δ films on (001) SrTiO3 were prepared by pulsed laser deposition and by reducing the oxygen pressure for deposition. The decrease in the magnitude of oxygen drives the transformation of Ce4+ to Ce3+ ion, restraining the appearance of CeO2 that usually exists as impurity in bulk La0.47Ce0.20Ca0.33MnO3. The magnetic transition temperature of the films increases with increasing the deposition oxygen pressure. The temperature dependence of the electrical resistance (R) of the single-phase films obeys the thermally activated behavior. A postannealing procedure was carried out on a film deposited in 0.4Pa. The magnetic transition temperature is markedly increased and R is dramatically decreased by annealing. A metal-insulator transition occurs at 217K with a magnetoresistance of −73% for the annealed film. This metal-insulator transition temperature is much higher than that of the bulk La0.47Ce0.20Ca0.33MnO3.
Physica B-condensed Matter | 2009
Wen Ren; Jiaqi Yang; B. Li; D. Li; X. G. Zhao; Z. D. Zhang