P57 Suppresses the Pluripotency and Proliferation of Mouse Embryonic Stem Cells by Positively Regulating P53 Activation

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2022 Jan 3

PMID 34976070

Citations 1

Authors

Na Li

Zhaoyu Du

YunXiang Li

Wenjing Xu

Yumei Yang

Haodong Peng

Tianxiang Song

Qihua Qin

Huining Lei

Jinlian Hua

Affiliations

Soon will be listed here.

Abstract

Embryonic stem cells (ESCs) are pluripotent stem cells that have indefinite self-renewal capacities under appropriate culture conditions . The pluripotency maintenance and proliferation of these cells are delicately governed by the concert effect of a complex transcriptional regulatory network. Herein, we discovered that p57 (p57), a cyclin-dependent kinase inhibitor canonically inhibiting cell proliferation, played a role in suppressing the pluripotency state of mouse ESCs (mESCs). p57 knockdown significantly stimulated the expressions of core pluripotency factors NANOG, OCT4, and SOX2, while p57 overexpression inhibited the expressions of these factors in mESCs. In addition, consistent with its function in somatic cells, p57 suppressed mESC proliferation. Further analysis showed that p57 could interact with and contribute to the activation of p53 in mESCs. In conclusion, the present study showed that p57 could antagonize the pluripotency state and the proliferation process of mESCs. This finding uncovers a novel function of p57 and provides new evidence for elucidating the complex regulatory of network of mESC fate.

Citing Articles

Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths.

Vainorius G, Novatchkova M, Michlits G, Baar J, Raupach C, Lee J Nat Commun. 2023; 14(1):5341.

PMID: 37660160 PMC: 10475046. DOI: 10.1038/s41467-023-40803-y.

References

Li N, Ma W, Shen Q, Zhang M, Du Z, Wu C . Reconstitution of male germline cell specification from mouse embryonic stem cells using defined factors in vitro. Cell Death Differ. 2019; 26(10):2115-2124. PMC: 6748084. DOI: 10.1038/s41418-019-0280-2. View

Pfurr S, Chu Y, Bohrer C, Greulich F, Beattie R, Mammadzada K . The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development. Development. 2017; 144(21):3917-3931. DOI: 10.1242/dev.145698. View

Lorzadeh N, Kazemirad N . Embryonic Stem Cells and Infertility. Am J Perinatol. 2018; 35(10):925-930. DOI: 10.1055/s-0038-1632367. View

Roeb W, Boyer A, Cavenee W, Arden K . PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1. Proc Natl Acad Sci U S A. 2007; 104(46):18085-90. PMC: 2084300. DOI: 10.1073/pnas.0708910104. View

Furutachi S, Matsumoto A, Nakayama K, Gotoh Y . p57 controls adult neural stem cell quiescence and modulates the pace of lifelong neurogenesis. EMBO J. 2013; 32(7):970-81. PMC: 3616292. DOI: 10.1038/emboj.2013.50. View

Coronado D, Godet M, Bourillot P, Tapponnier Y, Bernat A, Petit M . A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency. Stem Cell Res. 2012; 10(1):118-31. DOI: 10.1016/j.scr.2012.10.004. View

Matsuoka S, Edwards M, Bai C, Parker S, Zhang P, Baldini A . p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 1995; 9(6):650-62. DOI: 10.1101/gad.9.6.650. View

Wu D, Chen E, Tang H . Stem cell transplantation for the treatment of end-stage liver disease. World J Hepatol. 2019; 10(12):907-910. PMC: 6323519. DOI: 10.4254/wjh.v10.i12.907. View

Hall J, Guo G, Wray J, Eyres I, Nichols J, Grotewold L . Oct4 and LIF/Stat3 additively induce Krüppel factors to sustain embryonic stem cell self-renewal. Cell Stem Cell. 2009; 5(6):597-609. DOI: 10.1016/j.stem.2009.11.003. View

10.

Fan Y, Winanto , Ng S . Replacing what's lost: a new era of stem cell therapy for Parkinson's disease. Transl Neurodegener. 2020; 9:2. PMC: 6945567. DOI: 10.1186/s40035-019-0180-x. View

11.

Li Y, Xia W, der Merwe L, Dai W, Lin C . Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies. Stem Cell Res Ther. 2020; 11(1):322. PMC: 7389817. DOI: 10.1186/s13287-020-01839-9. View

12.

Sengupta S, Nie J, Wagner R, Yang C, Stewart R, Thomson J . MicroRNA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cells. Stem Cells. 2009; 27(7):1524-8. DOI: 10.1002/stem.84. View

13.

Barriga F, Montagni E, Mana M, Mendez-Lago M, Hernando-Momblona X, Sevillano M . Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells. Cell Stem Cell. 2017; 20(6):801-816.e7. PMC: 5774992. DOI: 10.1016/j.stem.2017.02.007. View

14.

Lee D, Su J, Ang Y, Carvajal-Vergara X, Mulero-Navarro S, Pereira C . Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling. Cell Stem Cell. 2012; 11(2):179-94. PMC: 3413175. DOI: 10.1016/j.stem.2012.05.020. View

15.

Zacharek S, Fillmore C, Lau A, Gludish D, Chou A, Ho J . Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci. Cell Stem Cell. 2011; 9(3):272-81. PMC: 3167236. DOI: 10.1016/j.stem.2011.07.007. View

16.

Simsa-Maziel S, Monsonego-Ornan E . Interleukin-1β promotes proliferation and inhibits differentiation of chondrocytes through a mechanism involving down-regulation of FGFR-3 and p21. Endocrinology. 2012; 153(5):2296-310. DOI: 10.1210/en.2011-1756. View

17.

Li J, Bei Y, Liu Q, Lv D, Xu T, He Y . MicroRNA-221 is required for proliferation of mouse embryonic stem cells via P57 targeting. Stem Cell Rev Rep. 2014; 11(1):39-49. DOI: 10.1007/s12015-014-9543-y. View

18.

Matsumoto A, Takeishi S, Kanie T, Susaki E, Onoyama I, Tateishi Y . p57 is required for quiescence and maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2011; 9(3):262-71. DOI: 10.1016/j.stem.2011.06.014. View

19.

Hassani S, Moradi S, Taleahmad S, Braun T, Baharvand H . Transition of inner cell mass to embryonic stem cells: mechanisms, facts, and hypotheses. Cell Mol Life Sci. 2018; 76(5):873-892. PMC: 11105545. DOI: 10.1007/s00018-018-2965-y. View

20.

Tury A, Mairet-Coello G, DiCicco-Bloom E . The cyclin-dependent kinase inhibitor p57Kip2 regulates cell cycle exit, differentiation, and migration of embryonic cerebral cortical precursors. Cereb Cortex. 2011; 21(8):1840-56. PMC: 3138513. DOI: 10.1093/cercor/bhq254. View