A MiR-372/let-7 Axis Regulates Human Germ Versus Somatic Cell Fates

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2016 Apr 13

PMID 27066911

Citations 15

Authors

Nam D Tran

Michael Kissner

Deepa Subramanyam

Ronald J Parchem

Diana J Laird

Robert H Blelloch

Affiliations

Soon will be listed here.

Abstract

The embryonic stem cell cycle (ESCC) and let-7 families of miRNAs function antagonistically in the switch between mouse embryonic stem cell self-renewal and somatic differentiation. Here, we report that the human ESCC miRNA miR-372 and let-7 act antagonistically in germline differentiation from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). hESC and iPSC-derived primordial germ cell-like cells (PGCLCs) expressed high levels of miR-372 and conversely, somatic cells expressed high levels of let-7. Manipulation of miRNA levels by introduction of miRNA mimics or knockdown with miRNA sponges demonstrated that miR-372 promotes whereas let-7 antagonizes PGCLC differentiation. Knockdown of the individual miR-372 targets SMARCC1, MECP2, CDKN1, RBL2, RHOC, and TGFBR2 increased PGCLC production, whereas knockdown of the let-7 targets CMYC and NMYC suppressed PGCLC differentiation. These findings uncover a miR-372/let-7 axis regulating human primordial germ cell (PGC) specification. Stem Cells 2016;34:1985-1991.

Citing Articles

miR-372-3p represses hepatic stellate cell activation via the RhoC/ROCK pathway.

Ou S, Tang X, Li Z, Ouyang R, Lei Y, Chen G Cytotechnology. 2025; 77(2):60.

PMID: 39959789 PMC: 11828770. DOI: 10.1007/s10616-025-00715-9.

Evaluation of the expression level of microRNA-21, microRNA-15a, microRNA-372 in human follicular fluid stem cells-derived oocyte-like cells (OLCs).

Saki G, Shahrooie K, Taheri Moghadam M, Eftekhari Moghadam A, Nikbakht R JBRA Assist Reprod. 2024; 28(2):289-294.

PMID: 38530760 PMC: 11152413. DOI: 10.5935/1518-0557.20240019.

MicroRNA-372 acts as a double-edged sword in human cancers.

Tajik F, Alian F, Yousefi M, Azadfallah A, Hoseini A, Mohammadi F Heliyon. 2023; 9(5):e15991.

PMID: 37251909 PMC: 10208947. DOI: 10.1016/j.heliyon.2023.e15991.

Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions.

Bure I, Nemtsova M Int J Mol Sci. 2023; 24(9).

PMID: 37175555 PMC: 10178202. DOI: 10.3390/ijms24097848.

Potential Biomarkers of miR-371-373 Gene Cluster in Tumorigenesis.

Shah J, Khattak S, Rauf M, Cai Y, Jin J Life (Basel). 2021; 11(9).

PMID: 34575133 PMC: 8465240. DOI: 10.3390/life11090984.

References

Worringer K, Rand T, Hayashi Y, Sami S, Takahashi K, Tanabe K . The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes. Cell Stem Cell. 2013; 14(1):40-52. PMC: 3982312. DOI: 10.1016/j.stem.2013.11.001. View

Gkountela S, Li Z, Vincent J, Zhang K, Chen A, Pellegrini M . The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation. Nat Cell Biol. 2012; 15(1):113-22. PMC: 3786872. DOI: 10.1038/ncb2638. View

Judson R, Babiarz J, Venere M, Blelloch R . Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat Biotechnol. 2009; 27(5):459-61. PMC: 2743930. DOI: 10.1038/nbt.1535. View

Judson H, Hayward B, Sheridan E, Bonthron D . A global disorder of imprinting in the human female germ line. Nature. 2002; 416(6880):539-42. DOI: 10.1038/416539a. View

Ebert M, Neilson J, Sharp P . MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007; 4(9):721-6. PMC: 3857099. DOI: 10.1038/nmeth1079. View

Subramanyam D, Lamouille S, Judson R, Liu J, Bucay N, Derynck R . Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat Biotechnol. 2011; 29(5):443-8. PMC: 3685579. DOI: 10.1038/nbt.1862. View

Tang W, Dietmann S, Irie N, Leitch H, Floros V, Bradshaw C . A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell. 2015; 161(6):1453-67. PMC: 4459712. DOI: 10.1016/j.cell.2015.04.053. View

Ma Y, Ramezani A, Lewis R, Hawley R, Thomson J . High-level sustained transgene expression in human embryonic stem cells using lentiviral vectors. Stem Cells. 2003; 21(1):111-7. DOI: 10.1634/stemcells.21-1-111. View

Hayashi K, Ogushi S, Kurimoto K, Shimamoto S, Ohta H, Saitou M . Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science. 2012; 338(6109):971-5. DOI: 10.1126/science.1226889. View

10.

West J, Viswanathan S, Yabuuchi A, Cunniff K, Takeuchi A, Park I . A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature. 2009; 460(7257):909-13. PMC: 2729657. DOI: 10.1038/nature08210. View

11.

Ohinata Y, Payer B, OCarroll D, Ancelin K, Ono Y, Sano M . Blimp1 is a critical determinant of the germ cell lineage in mice. Nature. 2005; 436(7048):207-13. DOI: 10.1038/nature03813. View

12.

Irie N, Weinberger L, Tang W, Kobayashi T, Viukov S, Manor Y . SOX17 is a critical specifier of human primordial germ cell fate. Cell. 2014; 160(1-2):253-68. PMC: 4310934. DOI: 10.1016/j.cell.2014.12.013. View

13.

Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R . DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007; 39(3):380-5. PMC: 3008549. DOI: 10.1038/ng1969. View

14.

Hayashi K, Ohta H, Kurimoto K, Aramaki S, Saitou M . Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell. 2011; 146(4):519-32. DOI: 10.1016/j.cell.2011.06.052. View

15.

Lacham-Kaplan O . In vivo and in vitro differentiation of male germ cells in the mouse. Reproduction. 2004; 128(2):147-52. DOI: 10.1530/rep.1.00220. View

16.

Melton C, Judson R, Blelloch R . Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature. 2010; 463(7281):621-6. PMC: 2894702. DOI: 10.1038/nature08725. View

17.

Medrano J, Ramathal C, Nguyen H, Simon C, Pera R . Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro. Stem Cells. 2011; 30(3):441-51. PMC: 3695740. DOI: 10.1002/stem.1012. View

18.

Yuan L, Liu J, Zhao J, Brundell E, Daneholt B, Hoog C . The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell. 2000; 5(1):73-83. DOI: 10.1016/s1097-2765(00)80404-9. View

19.

Durcova-Hills G, Tang F, Doody G, Tooze R, Surani M . Reprogramming primordial germ cells into pluripotent stem cells. PLoS One. 2008; 3(10):e3531. PMC: 2567847. DOI: 10.1371/journal.pone.0003531. View

20.

West F, Machacek D, Boyd N, Pandiyan K, Robbins K, Stice S . Enrichment and differentiation of human germ-like cells mediated by feeder cells and basic fibroblast growth factor signaling. Stem Cells. 2008; 26(11):2768-76. DOI: 10.1634/stemcells.2008-0124. View