Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

doi:10.1007/s13238-017-0470-y

Protein Cell

2018, Vol. 9

Issue (8) : 717-728 https://doi.org/10.1007/s13238-017-0470-y

RESEARCH ARTICLE

Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

Jinzhu Xiang¹, Suying Cao², Liang Zhong¹, Hanning Wang^1,⁵, Yangli Pei^1,⁶, Qingqing Wei¹, Bingqiang Wen¹, Haiyuan Mu¹, Shaopeng Zhang¹, Liang Yue¹, Genhua Yue³, Bing Lim⁴, Jianyong Han¹(

)

¹. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
². Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China
³. Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore
⁴. Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore
⁵. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China
⁶. State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Download: PDF(4218 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a “dose effect”. Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.

Keywords pluripotent stem cells 4-cell embryo injection secreted proteins Activin A chimeric mice

Corresponding Author(s): Jianyong Han

Issue Date: 14 August 2018

Cite this article:

Jinzhu Xiang,Suying Cao,Liang Zhong, et al. Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos[J]. Protein Cell, 2018, 9(8): 717-728.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-017-0470-y
https://academic.hep.com.cn/pac/EN/Y2018/V9/I8/717

1	Cockburn K, Rossant J (2010) Making the blastocyst: lessons from the mouse. J Clin Invest 120:995–1003 https://doi.org/10.1172/JCI41229
2	Eakin GS, Behringer RR (2003) Tetraploid development in the mouse. Dev Dyn 228:751–766 https://doi.org/10.1002/dvdy.10363
3	Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156 https://doi.org/10.1038/292154a0
4	Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang F, Huang Y (2015) Singlecell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol 16:148 https://doi.org/10.1186/s13059-015-0706-1
5	Ghimire S, Heindryckx B, Van der Jeught M, Neupane J, O’Leary T, Lierman S, De Vos WH, de Sousa Chuva, Lopes S, Deroo T, De Sutter P (2015) Inhibition of transforming growth factor beta signaling promotes epiblast formation in mouse embryos. Stem Cells Dev 24:497–506 https://doi.org/10.1089/scd.2014.0206
6	Guzman-Ayala M, Ben-Haim N, Beck S, Constam DB (2004) Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment. Proc Natl Acad Sci USA 101:15656–15660 https://doi.org/10.1073/pnas.0405429101
7	Han J, Yuan P, Yang H, Zhang J, Soh BS, Li P, Lim SL, Cao S, Tay J, Orlov YLet al. (2010) Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature 463:1096–1100 https://doi.org/10.1038/nature08735
8	Heng JCD, Feng B, Han JY, Jiang JM, Kraus P, Ng JH, Orlov YL, Huss M, Yang L, Lufkin Tet al. (2010) The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6:167–174 https://doi.org/10.1016/j.stem.2009.12.009
9	Huang J, Deng K, Wu H, Liu Z, Chen Z, Cao S, Zhou L, Ye X, Keefe DL, Liu L (2008) Efficient production of mice from embryonic stem cells injected into four- or eight-cell embryos by piezo micromanipulation. Stem Cells 26:1883–1890 https://doi.org/10.1634/stemcells.2008-0164
10	Humiecka M, Krupa M, Guzewska MM, Maleszewski M, Suwinska A (2016) ESCs injected into the 8-cell stage mouse embryo modify pattern of cleavage and cell lineage specification. Mech Dev 141:40–50 https://doi.org/10.1016/j.mod.2016.06.002
11	Inman GJ, Nicolas FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (2002) SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62:65–74 https://doi.org/10.1124/mol.62.1.65
12	Kang L, Wu T, Tao Y, Yuan Y, He J, Zhang Y, Luo T, Kou ZH, Gao SR (2011) Viable mice produced from three-factor induced pluripotent stem (iPS) cells through tetraploid complementation. Cell Res 21:546–549 https://doi.org/10.1038/cr.2010.164
13	Kawase Y, Iwata T, Watanabe M, Kamada N, Ueda O, Suzuki H (2001) Application of the piezo-micromanipulator for injection of embryonic stem cells into mouse blastocysts. Contemp Top Lab Anim Sci 40:31–34
14	Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch Ret al. (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70 https://doi.org/10.1016/j.stem.2007.05.014
15	Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638 https://doi.org/10.1073/pnas.78.12.7634
16	Ngangan AV, Waring JC, Cooke MT, Mandrycky CJ, McDevitt TC (2014) Soluble factors secreted by differentiating embryonic stem cells stimulate exogenous cell proliferation and migration. Stem Cell Res Ther 5:26 https://doi.org/10.1186/scrt415
17	Ohinata Y, Tsukiyama T (2014) Establishment of trophoblast stem cells under defined culture conditions in mice. PLoS ONE 9:e107308 https://doi.org/10.1371/journal.pone.0107308
18	Pauklin S, Vallier L (2015) Activin/Nodal signalling in stem cells. Development 142:607–619 https://doi.org/10.1242/dev.091769
19	Poueymirou WT, Auerbach W, Frendewey D, Hickey JF, Escaravage JM, Esau L, Dore AT, Stevens S, Adams NC, Dominguez MGet al. (2007) F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses. Nat Biotechnol 25:91–99 https://doi.org/10.1038/nbt1263
20	Ramirezsolis R, Davis AC, Bradley A (1993) Gene targeting in embryonic stem-cells. Method Enzymol 225:855–878 https://doi.org/10.1016/0076-6879(93)25054-6
21	Rossant J, Tam PP (2009) Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development 136:701–713 https://doi.org/10.1242/dev.017178
22	Stewart CL (1993) Production of chimeras between embryonic stemcells and embryos. Method Enzymol 225:823–855 https://doi.org/10.1016/0076-6879(93)25053-5
23	Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cellsfrom mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676 https://doi.org/10.1016/j.cell.2006.07.024
24	Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872 https://doi.org/10.1016/j.cell.2007.11.019
25	Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem-cells. Cell 51:503–512 https://doi.org/10.1016/0092-8674(87)90646-5
26	Vintersten K, Monetti C, Gertsenstein M, Zhang P, Laszlo L, Biechele S, Nagy A (2004) Mouse in red: red fluorescent protein expression in mouse ES cells, embryos, and adult animals. Genesis 40:241–246 https://doi.org/10.1002/gene.20095
27	Wang H, Dey SK (2006) Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet 7:185–199 https://doi.org/10.1038/nrg1808
28	Wernig M, Meissner A, Foreman R, Brambrink T, Ku MC, Hochedlinger K, Bernstein BE, Jaenisch R (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:318 https://doi.org/10.1038/nature05944
29	Yousef H, Conboy MJ, Mamiya H, Zeiderman M, Schlesinger C, Schaffer DV, Conboy IM (2014) Mechanisms of action of hESCsecreted proteins that enhance human and mouse myogenesis. Aging 6:602–620 https://doi.org/10.18632/aging.100659
30	Zernicka-Goetz M, Morris SA, Bruce AW (2009) Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo. Nat Rev Genet 10:467–477 https://doi.org/10.1038/nrg2564
31	Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, Hao J, Guo CL, Ma QW, Wang Let al. (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461:86 https://doi.org/10.1038/nature08267

[1]

PAC-0717-17203-HJY_suppl_1

Download

[1]	Xuemei Fu, Shouhai Wu, Bo Li, Yang Xu, Jingfeng Liu. Functions of p53 in pluripotent stem cells[J]. Protein Cell, 2020, 11(1): 71-78.
[2]	Feng Li, Yuanlong Ge, Dan Liu, Zhou Songyang. The role of telomere-binding modulators in pluripotent stem cells[J]. Protein Cell, 2020, 11(1): 60-70.
[3]	Jianying Guo, Dacheng Ma, Rujin Huang, Jia Ming, Min Ye, Kehkooi Kee, Zhen Xie, Jie Na. An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells[J]. Protein Cell, 2017, 8(5): 379-393.
[4]	Qianqian Liang,Chen Xu,Xinyun Chen,Xiuya Li,Chao Lu,Ping Zhou,Lianhua Yin,Ruizhe Qian,Sifeng Chen,Zhendong Ling,Ning Sun. The roles of Mesp family proteins: functional diversity and redundancy in differentiation of pluripotent stem cells and mammalian mesodermal development[J]. Protein Cell, 2015, 6(8): 553-561.
[5]	Jie Na,Duncan Baker,Jing Zhang,Peter W. Andrews,Ivana Barbaric. Aneuploidy in pluripotent stem cells and implications for cancerous transformation[J]. Protein Cell, 2014, 5(8): 569-579.
[6]	Yan Huang,Puping Liang,Dan Liu,Junjiu Huang,Zhou Songyang. Telomere regulation in pluripotent stem cells[J]. Protein Cell, 2014, 5(3): 194-202.
[7]	Rui Li, Ye Bai, Tongtong Liu, Xiaoqun Wang, Qian Wu. Induced pluripotency and direct reprogramming: a new window for treatment of neurodegenerative diseases[J]. Prot Cell, 2013, 4(6): 415-424.
[8]	Tao Wang, Stephen T. Warren, Peng Jin. Toward pluripotency by reprogramming: mechanisms and application[J]. Prot Cell, 2013, 4(11): 820-832.
[9]	Fei Yi, Guang-Hui Liu, Juan Carlos Izpisua Belmonte. Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy[J]. Prot Cell, 2012, 3(4): 246-250.
[10]	Zhao Chen, Tongbiao Zhao, Yang Xu. The genomic stability of induced pluripotent stem cells[J]. Prot Cell, 2012, 3(4): 271-277.
[11]	Yuan Jiang, Mei-Jiang Zhang, Bao-Yang Hu. Specification of functional neurons and glia from human pluripotent stem cells[J]. Prot Cell, 2012, 3(11): 818-825.
[12]	Qihui Wang, Xiaoning Mou, Henghua Cao, Qingzhang Meng, Yanni Ma, Pengcheng Han, Junjie Jiang, Hao Zhang, Yue Ma. A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture[J]. Prot Cell, 2012, 3(1): 51-59.
[13]	Changhai Tian, Yongxiang Wang, Lijun Sun, Kangmu Ma, Jialin C. Zheng. Reprogrammed mouse astrocytes retain a “memory” of tissue origin and possess more tendencies for neuronal differentiation than reprogrammed mouse embryonic fibroblasts[J]. Prot Cell, 2011, 2(2): 128-140.
[14]	Peizhe Wang, Jie Na. Mechanism and methods to induce pluripotency[J]. Prot Cell, 2011, 2(10): 792-799.

Viewed

Full text

Abstract

Cited

Shared

Discussed