TY - JOUR
T1 - Specification and epigenomic resetting of the pig germline exhibit conservation with the human lineage
AU - Zhu, Qifan
AU - Sang, Fei
AU - Withey, Sarah
AU - Tang, Walfred
AU - Dietmann, Sabine
AU - Klisch, Doris
AU - Ramos-Ibeas, Priscila
AU - Zhang, Haixin
AU - Requena, Cristina E.
AU - Hajkova, Petra
AU - Loose, Matt
AU - Surani, M. Azim
AU - Alberio, Ramiro
N1 - Funding Information:
Q.Z. was funded by China Scholarship Council and The University of Nottingham . P.R.-I. was funded by a Marie Sklodowska Curie fellowship (grant 654609 ) and Ramon y Cajal ( RYC2018-025666-I ). W.W.C.T. was supported by the Croucher Foundation . P.H. acknowledges MRC ( MC_US_A652_5PY70 ) and the ERC ( ERC-CoG- 648879 ). M.A.S. is supported by a Wellcome Investigator Award, MRC , and core funding from Wellcome-CRUK to the Gurdon Institute. This work was supported by the Biotechnology and Biological Sciences Research Council ( BB/M001466/1 to R.A. and M.A.S.).
Funding Information:
Q.Z. was funded by China Scholarship Council and The University of Nottingham. P.R.-I. was funded by a Marie Sklodowska Curie fellowship (grant 654609) and Ramon y Cajal (RYC2018-025666-I). W.W.C.T. was supported by the Croucher Foundation. P.H. acknowledges MRC (MC_US_A652_5PY70) and the ERC (ERC-CoG- 648879). M.A.S. is supported by a Wellcome Investigator Award, MRC, and core funding from Wellcome-CRUK to the Gurdon Institute. This work was supported by the Biotechnology and Biological Sciences Research Council (BB/M001466/1 to R.A. and M.A.S.). Q.Z. S.W. P.R.-I. D.K. and H.Z. performed experiments, including FACS, IF, scRNA-seq, and embryo dissection. Q.Z. and F.S. performed bioinformatics analyses with supervision from M.L. S.D. performed DNA methylation analyses. W.T. contributed to WGBS and scRNA-seq protocols and analyses. C.E.R. and P.H. performed LC-MS/MS experiments. R.A. supervised the project and performed dissections. R.A. and M.A.S. designed experiments, conceived the project, and, together with Q.Z. wrote the paper. All authors discussed the results and contributed to the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2021 The Authors
PY - 2021/2/9
Y1 - 2021/2/9
N2 - Investigations of the human germline and programming are challenging because of limited access to embryonic material. However, the pig as a model may provide insights into transcriptional network and epigenetic reprogramming applicable to both species. Here we show that, during the pre- and early migratory stages, pig primordial germ cells (PGCs) initiate large-scale epigenomic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and, potentially, base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3 as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, including in vitro gametogenesis.
AB - Investigations of the human germline and programming are challenging because of limited access to embryonic material. However, the pig as a model may provide insights into transcriptional network and epigenetic reprogramming applicable to both species. Here we show that, during the pre- and early migratory stages, pig primordial germ cells (PGCs) initiate large-scale epigenomic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and, potentially, base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3 as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, including in vitro gametogenesis.
KW - DNA demethylation
KW - X-chromosome reactivation
KW - epigenetic resetting
KW - escapees
KW - germ cells
KW - pig
KW - single-cell RNA-seq
KW - transgenerational inheritance
UR - http://www.scopus.com/inward/record.url?scp=85100462059&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2021.108735
DO - 10.1016/j.celrep.2021.108735
M3 - Article
C2 - 33567277
AN - SCOPUS:85100462059
SN - 2211-1247
VL - 34
JO - Cell Reports
JF - Cell Reports
IS - 6
M1 - 108735
ER -