PIWI Proteins Are Dispensable for Mouse Somatic Development and Reprogramming of Fibroblasts into Pluripotent Stem Cells

Cheng, Ee-Chun; Kang, Dongwan; Wang, Zhong; Lin, Haifan

doi:10.1371/journal.pone.0097821

Title: PIWI Proteins Are Dispensable for Mouse Somatic Development and Reprogramming of Fibroblasts into Pluripotent Stem Cells

Journal Article · Fri Sep 19 00:00:00 EDT 2014 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0097821· OSTI ID:1627700

Cheng, Ee-Chun ^[1]; Kang, Dongwan ^[2]; Wang, Zhong ^[2]; Lin, Haifan ^[1]

Yale Univ., New Haven, CT (United States). School of Medicine. Dept. of Cell Biology. Yale Stem Cell Center
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division

PIWI proteins play essential and conserved roles in germline development, including germline stem cell maintenance and meiosis. Because germline regulators such as OCT4, NANOG, and SOX2 are known to be potent factors that reprogram differentiated somatic cells into induced pluripotent stem cells (iPSCs), we investigated whether the PIWI protein family is involved in iPSC production. We find that all three mouse Piwi genes, Miwi, Mili, and Miwi2, are expressed in embryonic stem cells (ESCs) at higher levels than in fibroblasts, with Mili being the highest. However, mice lacking all three Piwi genes are viable and female fertile, and are only male sterile. Furthermore, embryonic fibroblasts derived from Miwi/Mili/Miwi2 triple knockout embryos can be efficiently reprogrammed into iPS cells. These iPS cells expressed pluripotency markers and were capable of differentiating into all three germ layers in teratoma assays. Genome-wide expression profiling reveals that the triple knockout iPS cells are very similar to littermate control iPS cells. These results indicate that PIWI proteins are dispensable for direct reprogramming of mouse fibroblasts.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627700

Journal Information:: PLoS ONE, Vol. 9, Issue 9; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (64)

LIN28 lets BLIMP1 Take the Right Course Matzuk, Martin M. Developmental Cell, Vol. 17, Issue 2 https://doi.org/10.1016/j.devcel.2009.07.020	journal	August 2009
Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic Cells Brambrink, Tobias; Foreman, Ruth; Welstead, G. Grant Cell Stem Cell, Vol. 2, Issue 2 https://doi.org/10.1016/j.stem.2008.01.004	journal	February 2008
Isolation and characterization of human spermatogonial stem cells Liu, Shixue; Tang, Ziwei; Xiong, Tao Reproductive Biology and Endocrinology, Vol. 9, Issue 1 https://doi.org/10.1186/1477-7827-9-141	journal	January 2011
MIWI2 Is Essential for Spermatogenesis and Repression of Transposons in the Mouse Male Germline Carmell, Michelle A.; Girard, Angélique; van de Kant, Henk J. G. Developmental Cell, Vol. 12, Issue 4 https://doi.org/10.1016/j.devcel.2007.03.001	journal	April 2007
Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation Gangaraju, Vamsi K.; Yin, Hang; Weiner, Molly M. Nature Genetics, Vol. 43, Issue 2 https://doi.org/10.1038/ng.743	journal	December 2010
Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates Ma, Ziyang; Swigut, Tomek; Valouev, Anton Nature Structural & Molecular Biology, Vol. 18, Issue 2 https://doi.org/10.1038/nsmb.2000	journal	December 2010
MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation Unhavaithaya, Yingdee; Hao, Yi; Beyret, Ergin Journal of Biological Chemistry, Vol. 284, Issue 10 https://doi.org/10.1074/jbc.M809104200	journal	March 2009
A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice Aravin, Alexei A.; Sachidanandam, Ravi; Bourc'his, Deborah Molecular Cell, Vol. 31, Issue 6 https://doi.org/10.1016/j.molcel.2008.09.003	journal	September 2008
Beyond transposons: the epigenetic and somatic functions of the Piwi-piRNA mechanism Peng, Jamy C.; Lin, Haifan Current Opinion in Cell Biology, Vol. 25, Issue 2 https://doi.org/10.1016/j.ceb.2013.01.010	journal	April 2013
Rats and mice share common ethologically relevant parameters of exploratory behavior Drai, Dan; Kafkafi, Neri; Benjamini, Yoav Behavioural Brain Research, Vol. 125, Issue 1-2 https://doi.org/10.1016/s0166-4328(01)00290-x	journal	November 2001
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells Yu, J.; Vodyanik, M. A.; Smuga-Otto, K. Science, Vol. 318, Issue 5858 https://doi.org/10.1126/science.1151526	journal	December 2007
Fast and accurate short read alignment with Burrows-Wheeler transform Li, H.; Durbin, R. Bioinformatics, Vol. 25, Issue 14 https://doi.org/10.1093/bioinformatics/btp324	journal	May 2009
Embryonic Stem Cell Self-Renewal, Analyzed Temple, Sally Cell, Vol. 115, Issue 3 https://doi.org/10.1016/s0092-8674(03)00853-5	journal	October 2003
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 Huangfu, Danwei; Osafune, Kenji; Maehr, René Nature Biotechnology, Vol. 26, Issue 11 https://doi.org/10.1038/nbt.1502	journal	October 2008
Generation of multipotent cell lines from a distinct population of male germ line stem cells Izadyar, Fariborz; Pau, Francis; Marh, Joel REPRODUCTION, Vol. 135, Issue 6 https://doi.org/10.1530/rep-07-0479	journal	June 2008
Differential expression analysis for sequence count data Anders, Simon; Huber, Wolfgang Genome Biology, Vol. 11, Issue 10 https://doi.org/10.1186/gb-2010-11-10-r106	journal	October 2010
Pathway to Totipotency: Lessons from Germ Cells Seydoux, Geraldine; Braun, Robert E. Cell, Vol. 127, Issue 5 https://doi.org/10.1016/j.cell.2006.11.016	journal	December 2006
The Role of PIWI and the miRNA Machinery in Drosophila Germline Determination Megosh, Heather B.; Cox, Daniel N.; Campbell, Chris Current Biology, Vol. 16, Issue 19 https://doi.org/10.1016/j.cub.2006.08.051	journal	October 2006
Drosophila PIWI associates with chromatin and interacts directly with HP1a Brower-Toland, B.; Findley, S. D.; Jiang, L. Genes & Development, Vol. 21, Issue 18 https://doi.org/10.1101/gad.1564307	journal	September 2007
Suppression of SHP-2 and ERK Signalling Promotes Self-Renewal of Mouse Embryonic Stem Cells Burdon, Tom; Stracey, Craig; Chambers, Ian Developmental Biology, Vol. 210, Issue 1 https://doi.org/10.1006/dbio.1999.9265	journal	June 1999
Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1 Maekawa, Momoko; Yamaguchi, Kei; Nakamura, Tomonori Nature, Vol. 474, Issue 7350 https://doi.org/10.1038/nature10106	journal	June 2011
Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability Kirino, Yohei; Kim, Namwoo; de Planell-Saguer, Mariàngels Nature Cell Biology, Vol. 11, Issue 5 https://doi.org/10.1038/ncb1872	journal	April 2009
A Distinct Expression Pattern in Mammalian Testes Indicates a Conserved Role for NANOG in Spermatogenesis Kuijk, Ewart W.; de Gier, Jeffrey; Chuva de Sousa Lopes, Susana M. PLoS ONE, Vol. 5, Issue 6 https://doi.org/10.1371/journal.pone.0010987	journal	June 2010
A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal Cox, D. N.; Chao, A.; Baker, J. Genes & Development, Vol. 12, Issue 23 https://doi.org/10.1101/gad.12.23.3715	journal	December 1998
Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds Huangfu, Danwei; Maehr, René; Guo, Wenjun Nature Biotechnology, Vol. 26, Issue 7 https://doi.org/10.1038/nbt1418	journal	June 2008
Long-term proliferation of mouse primordial germ cells in culture Resnick, James L.; Bixler, Lynn S.; Cheng, Linzhao Nature, Vol. 359, Issue 6395 https://doi.org/10.1038/359550a0	journal	October 1992
Differential expression analysis for sequence count data Anders, Simon; Huber, Wolfgang Nature Precedings https://doi.org/10.1038/npre.2010.4282.2	journal	April 2010
Combining competition assays with genetic complementation strategies to dissect mouse embryonic stem cell self-renewal and pluripotency Lee, Dung-Fang; Su, Jie; Sevilla, Ana Nature Protocols, Vol. 7, Issue 4 https://doi.org/10.1038/nprot.2012.018	journal	March 2012
The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse Zheng, Ke; Wu, Xin; Kaestner, Klaus H. BMC Developmental Biology, Vol. 9, Issue 1 https://doi.org/10.1186/1471-213x-9-38	journal	January 2009
Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors Takahashi, Kazutoshi; Yamanaka, Shinya Cell, Vol. 126, Issue 4 https://doi.org/10.1016/j.cell.2006.07.024	journal	August 2006
baySeq: Empirical Bayesian methods for identifying differential expression in sequence count data Hardcastle, Thomas J.; Kelly, Krystyna A. BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-422	journal	August 2010
Identification and Regulation of a Stage-Specific Stem Cell Niche Enriched by Nanog-Positive Spermatogonial Stem Cells in the Mouse Testis: Pluripotent Spermatogonial Stem Cell Ventelä, Sami; Mäkelä, Juho-Antti; Kulmala, Jarmo STEM CELLS, Vol. 30, Issue 5 https://doi.org/10.1002/stem.1077	journal	April 2012
The Biogenesis and Function of PIWI Proteins and piRNAs: Progress and Prospect Thomson, Travis; Lin, Haifan Annual Review of Cell and Developmental Biology, Vol. 25, Issue 1 https://doi.org/10.1146/annurev.cellbio.24.110707.175327	journal	November 2009
Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation Grabole, Nils; Tischler, Julia; Hackett, Jamie A. EMBO reports, Vol. 14, Issue 7 https://doi.org/10.1038/embor.2013.67	journal	May 2013
Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis Vourekas, Anastassios; Zheng, Qi; Alexiou, Panagiotis Nature Structural & Molecular Biology, Vol. 19, Issue 8 https://doi.org/10.1038/nsmb.2347	journal	July 2012
Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis Anderson, Richard A.; Fulton, Norma; Cowan, Gillian BMC Developmental Biology, Vol. 7, Issue 1 https://doi.org/10.1186/1471-213X-7-136	journal	January 2007
aubergineencodes aDrosophilapolar granule component required for pole cell formation and related to eIF2C Harris, Adam N.; Macdonald, Paul M. Development, Vol. 128, Issue 14 https://doi.org/10.1242/dev.128.14.2823	journal	July 2001
A germ cell origin of embryonic stem cells? Zwaka, T. P. Development, Vol. 132, Issue 2 https://doi.org/10.1242/dev.01586	journal	January 2005
Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor Sato, Noboru; Meijer, Laurent; Skaltsounis, Leandros Nature Medicine, Vol. 10, Issue 1 https://doi.org/10.1038/nm979	journal	December 2003
Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3 Niwa, H.; Burdon, T.; Chambers, I. Genes & Development, Vol. 12, Issue 13 https://doi.org/10.1101/gad.12.13.2048	journal	July 1998
Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture Matsui, Yasuhisa; Zsebo, Krisztina; Hogan, Brigid L. M. Cell, Vol. 70, Issue 5 https://doi.org/10.1016/0092-8674(92)90317-6	journal	September 1992
PIWI proteins are essential for early Drosophila embryogenesis Mani, Sneha Ramesh; Megosh, Heather; Lin, Haifan Developmental Biology, Vol. 385, Issue 2 https://doi.org/10.1016/j.ydbio.2013.10.017	journal	January 2014
Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice Nolde, Mona J.; Cheng, Ee-chun; Guo, Shangqin PLoS ONE, Vol. 8, Issue 8 https://doi.org/10.1371/journal.pone.0071950	journal	August 2013
Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells Hayashi, Katsuhiko; Ohta, Hiroshi; Kurimoto, Kazuki Cell, Vol. 146, Issue 4 https://doi.org/10.1016/j.cell.2011.06.052	journal	August 2011
Uniting Germline and Stem Cells: The Function of Piwi Proteins and the piRNA Pathway in Diverse Organisms Juliano, Celina; Wang, Jianquan; Lin, Haifan Annual Review of Genetics, Vol. 45, Issue 1 https://doi.org/10.1146/annurev-genet-110410-132541	journal	December 2011
RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis Hong, Fangxin; Breitling, Rainer; McEntee, Connor W. Bioinformatics, Vol. 22, Issue 22 https://doi.org/10.1093/bioinformatics/btl476	journal	September 2006
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Robinson, M. D.; McCarthy, D. J.; Smyth, G. K. Bioinformatics, Vol. 26, Issue 1 https://doi.org/10.1093/bioinformatics/btp616	journal	November 2009
A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity Chia, Na-Yu; Chan, Yun-Shen; Feng, Bo Nature, Vol. 468, Issue 7321 https://doi.org/10.1038/nature09531	journal	October 2010
An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster Yin, Hang; Lin, Haifan Nature, Vol. 450, Issue 7167 https://doi.org/10.1038/nature06263	journal	October 2007
Induction of pluripotent stem cells from fibroblast cultures Takahashi, Kazutoshi; Okita, Keisuke; Nakagawa, Masato Nature Protocols, Vol. 2, Issue 12 https://doi.org/10.1038/nprot.2007.418	journal	November 2007
Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons Specchia, Valeria; Piacentini, Lucia; Tritto, Patrizia Nature, Vol. 463, Issue 7281 https://doi.org/10.1038/nature08739	journal	January 2010
Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis: Pluripotency factors and germ-cell (tumour)s Gillis, A. J. M.; Stoop, H.; Biermann, K. International Journal of Andrology, Vol. 34, Issue 4pt2 https://doi.org/10.1111/j.1365-2605.2011.01148.x	journal	June 2011
Controlling the false discovery rate in behavior genetics research Benjamini, Yoav; Drai, Dan; Elmer, Greg Behavioural Brain Research, Vol. 125, Issue 1-2 https://doi.org/10.1016/S0166-4328(01)00297-2	journal	November 2001
piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells Cox, D. N.; Chao, A.; Lin, H. Development, Vol. 127, Issue 3 https://doi.org/10.1242/dev.127.3.503	journal	February 2000
Long Live Sox2: Sox2 Lasts a Lifetime Driessens, Grégory; Blanpain, Cédric Cell Stem Cell, Vol. 9, Issue 4 https://doi.org/10.1016/j.stem.2011.09.007	journal	October 2011
BMP Induction of Id Proteins Suppresses Differentiation and Sustains Embryonic Stem Cell Self-Renewal in Collaboration with STAT3 Ying, Qi-Long; Nichols, Jennifer; Chambers, Ian Cell, Vol. 115, Issue 3 https://doi.org/10.1016/S0092-8674(03)00847-X	journal	October 2003
Germline Specification: Small Things Have a Big Role Jin, Zhigang; Xie, Ting Current Biology, Vol. 16, Issue 22 https://doi.org/10.1016/j.cub.2006.10.018	journal	November 2006
MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation Unhavaithaya, Yingdee; Hao, Yi; Beyret, Ergin Journal of Biological Chemistry, Vol. 284, Issue 10, 6507-6519 https://doi.org/10.3410/f.1157685.617895	journal	March 2009
Mili, a mammalian member of piwi family gene, is essential for spermatogenesis Kuramochi-Miyagawa, S. Development, Vol. 131, Issue 4 https://doi.org/10.1242/dev.00973	journal	January 2004
miwi, a Murine Homolog of piwi, Encodes a Cytoplasmic Protein Essential for Spermatogenesis Deng, Wei; Lin, Haifan Developmental Cell, Vol. 2, Issue 6 https://doi.org/10.1016/s1534-5807(02)00165-x	journal	June 2002
Sox2+ Adult Stem and Progenitor Cells Are Important for Tissue Regeneration and Survival of Mice Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna Cell Stem Cell, Vol. 9, Issue 4 https://doi.org/10.1016/j.stem.2011.09.001	journal	October 2011
Gene Expression Dynamics During Germline Specification in Mice Identified by Quantitative Single-Cell Gene Expression Profiling1 Yabuta, Yukihiro; Kurimoto, Kazuki; Ohinata, Yasuhide Biology of Reproduction, Vol. 75, Issue 5 https://doi.org/10.1095/biolreprod.106.053686	journal	November 2006
A Germ Cell-specific Gene, Prmt5, Works in Somatic Cell Reprogramming* Nagamatsu, Go; Kosaka, Takeo; Kawasumi, Miyuri Journal of Biological Chemistry, Vol. 286, Issue 12 https://doi.org/10.1074/jbc.m110.216390	journal	March 2011
Stem cells to help the heart Sharma, Arun Science, Vol. 367, Issue 6483 https://doi.org/10.1126/science.aba6111	journal	March 2020

Cited By (6)

Exploring the read-write genome: mobile DNA and mammalian adaptation Shapiro, James A. Critical Reviews in Biochemistry and Molecular Biology, Vol. 52, Issue 1 https://doi.org/10.1080/10409238.2016.1226748	journal	September 2016
Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte: Function of Somatic MIWI2 Shi, Xiaojie; Xiao, Zipei; Zonta, Francesco STEM CELLS, Vol. 37, Issue 6 https://doi.org/10.1002/stem.2994	journal	February 2019
Differential expression of piRNAs in reprogrammed pluripotent stem cells from mouse embryonic fibroblasts Zhu, Yanye; Fan, Chunsun; Zhao, Botao IUBMB Life, Vol. 71, Issue 12 https://doi.org/10.1002/iub.2128	journal	July 2019
Comparative Principles of DNA Methylation Reprogramming during Human and Mouse In Vitro Primordial Germ Cell Specification von Meyenn, Ferdinand; Berrens, Rebecca V.; Andrews, Simon Developmental Cell, Vol. 57, Issue 23 https://doi.org/10.1016/j.devcel.2022.11.009	journal	December 2022
Somatic expression of piRNA and associated machinery in the mouse identifies short, tissue-specific piRNA Perera, Bambarendage P. U.; Tsai, Zing Tsung-Yeh; Colwell, Mathia L. Epigenetics, Vol. 14, Issue 5 https://doi.org/10.1080/15592294.2019.1600389	journal	April 2019
Argonaute and Argonaute-Bound Small RNAs in Stem Cells Zhai, Lihong; Wang, Lin; Teng, Feng International Journal of Molecular Sciences, Vol. 17, Issue 2 https://doi.org/10.3390/ijms17020208	journal	February 2016

Similar Records

Generation and periodontal differentiation of human gingival fibroblasts-derived integration-free induced pluripotent stem cells

Journal Article · Fri May 06 00:00:00 EDT 2016 · Biochemical and Biophysical Research Communications · OSTI ID:1627700

Yin, Xiaohui; Li, Yang; Li, Jingwen; +4 more

Insulin receptor-mediated signaling regulates pluripotency markers and lineage differentiation

Journal Article · Sat Dec 01 00:00:00 EST 2018 · Molecular Metabolism · OSTI ID:1627700

Gupta, Manoj K.; De Jesus, Dario F.; Kahraman, Sevim; +7 more

Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

Journal Article · Mon Mar 30 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1627700

Hayashi, Yohei; Caboni, Laura; Das, Debanu; +16 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Science & Technology - Other Topics

Title: PIWI Proteins Are Dispensable for Mouse Somatic Development and Reprogramming of Fibroblasts into Pluripotent Stem Cells

Citation Formats

References (64)

Cited By (6)

Similar Records

Related Subjects