Zscan4 Transiently Reactivates Early Embryonic Genes During the Generation of Induced Pluripotent Stem Cells

Overview

Journal Sci Rep

Specialty Science

Date 2012 Feb 23

PMID 22355722

Citations 58

Authors

Tetsuya Hirata

Tomokazu Amano

Yuhki Nakatake

Misa Amano

Yulan Piao

Hien G Hoang

Minoru S H Ko

Affiliations

Soon will be listed here.

Abstract

The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required onlyfor the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

Citing Articles

DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells.

Rich J, Bennaroch M, Notel L, Patalakh P, Alberola J, Issa F EMBO Mol Med. 2024; 16(8):1840-1885.

PMID: 39009887 PMC: 11319797. DOI: 10.1038/s44321-024-00097-z.

Reprogramming Chromosome Ends by Functional Histone Acetylation.

Meltzer W, Gupta A, Lin P, Brown R, Benyamien-Roufaeil D, Khatri R Int J Mol Sci. 2024; 25(7).

PMID: 38612707 PMC: 11011970. DOI: 10.3390/ijms25073898.

ZSCAN4-binding motif-TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes.

Akiyama T, Ishiguro K, Chikazawa N, Ko S, Yukawa M, Ko M DNA Res. 2023; 31(1).

PMID: 38153767 PMC: 10785592. DOI: 10.1093/dnares/dsad029.

Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos.

Li X, Sun M, Jiang W, Zhou D, Lee S, Heo G Int J Mol Sci. 2023; 24(15).

PMID: 37569497 PMC: 10418334. DOI: 10.3390/ijms241512121.

Zfp296 knockout enhances chromatin accessibility and induces a unique state of pluripotency in embryonic stem cells.

Miyazaki S, Yamano H, Motooka D, Tashiro F, Matsuura T, Miyazaki T Commun Biol. 2023; 6(1):771.

PMID: 37488353 PMC: 10366109. DOI: 10.1038/s42003-023-05148-8.

References

Woltjen K, Michael I, Mohseni P, Desai R, Mileikovsky M, Hamalainen R . piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. 2009; 458(7239):766-70. PMC: 3758996. DOI: 10.1038/nature07863. View

Gonzalez F, Boue S, Izpisua Belmonte J . Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat Rev Genet. 2011; 12(4):231-42. DOI: 10.1038/nrg2937. View

Sridharan R, Tchieu J, Mason M, Yachechko R, Kuoy E, Horvath S . Role of the murine reprogramming factors in the induction of pluripotency. Cell. 2009; 136(2):364-77. PMC: 3273494. DOI: 10.1016/j.cell.2009.01.001. View

Nishiyama A, Xin L, Sharov A, Thomas M, Mowrer G, Meyers E . Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009; 5(4):420-33. PMC: 2770715. DOI: 10.1016/j.stem.2009.07.012. View

Sharov A, Nishiyama A, Piao Y, Correa-Cerro L, Amano T, Thomas M . Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity. BMC Genomics. 2011; 12:102. PMC: 3044670. DOI: 10.1186/1471-2164-12-102. View

Hanna J, Saha K, Pando B, van Zon J, Lengner C, Creyghton M . Direct cell reprogramming is a stochastic process amenable to acceleration. Nature. 2009; 462(7273):595-601. PMC: 2789972. DOI: 10.1038/nature08592. View

Koche R, Smith Z, Adli M, Gu H, Ku M, Gnirke A . Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell. 2011; 8(1):96-105. PMC: 3220622. DOI: 10.1016/j.stem.2010.12.001. View

Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S . Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A. 2010; 107(32):14152-7. PMC: 2922531. DOI: 10.1073/pnas.1009374107. View

Wilmut I, Schnieke A, McWhir J, Kind A, Campbell K . Viable offspring derived from fetal and adult mammalian cells. Nature. 1997; 385(6619):810-3. DOI: 10.1038/385810a0. View

10.

Brambrink T, Foreman R, Welstead G, Lengner C, Wernig M, Suh H . Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell. 2008; 2(2):151-9. PMC: 2276627. DOI: 10.1016/j.stem.2008.01.004. View

11.

Saeed A, Bhagabati N, Braisted J, Liang W, Sharov V, Howe E . TM4 microarray software suite. Methods Enzymol. 2006; 411:134-93. DOI: 10.1016/S0076-6879(06)11009-5. View

12.

Plath K, Lowry W . Progress in understanding reprogramming to the induced pluripotent state. Nat Rev Genet. 2011; 12(4):253-65. PMC: 3273493. DOI: 10.1038/nrg2955. View

13.

Silva J, Nichols J, Theunissen T, Guo G, van Oosten A, Barrandon O . Nanog is the gateway to the pluripotent ground state. Cell. 2009; 138(4):722-37. PMC: 3437554. DOI: 10.1016/j.cell.2009.07.039. View

14.

Wernig M, Lengner C, Hanna J, Lodato M, Steine E, Foreman R . A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 2008; 26(8):916-24. PMC: 2654269. DOI: 10.1038/nbt1483. View

15.

Stadtfeld M, Hochedlinger K . Induced pluripotency: history, mechanisms, and applications. Genes Dev. 2010; 24(20):2239-63. PMC: 2956203. DOI: 10.1101/gad.1963910. View

16.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

17.

Samavarchi-Tehrani P, Golipour A, David L, Sung H, Beyer T, Datti A . Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell. 2010; 7(1):64-77. DOI: 10.1016/j.stem.2010.04.015. View

18.

Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991; 108(2):193-9. DOI: 10.1016/0378-1119(91)90434-d. View

19.

Mayshar Y, Ben-David U, Lavon N, Biancotti J, Yakir B, Clark A . Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell. 2010; 7(4):521-31. DOI: 10.1016/j.stem.2010.07.017. View

20.

Eggan K, Akutsu H, Loring J, Klemm M, Rideout 3rd W, Yanagimachi R . Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci U S A. 2001; 98(11):6209-14. PMC: 33447. DOI: 10.1073/pnas.101118898. View