Blimp1/Prdm1 Governs Terminal Differentiation of Endovascular Trophoblast Giant Cells and Defines Multipotent Progenitors in the Developing Placenta

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2012 Sep 19

PMID 22987638

Citations 42

Authors

Arne Mould

Marc A J Morgan

Li Li

Elizabeth K Bikoff

Elizabeth J Robertson

Affiliations

Soon will be listed here.

Abstract

Developmental arrest of Blimp1/Prdm1 mutant embryos at around embryonic day 10.5 (E10.5) has been attributed to placental disturbances. Here we investigate Blimp1/Prdm1 requirements in the trophoblast cell lineage. Loss of function disrupts specification of the invasive spiral artery-associated trophoblast giant cells (SpA-TGCs) surrounding maternal blood vessels and severely compromises the ability of the spongiotrophoblast layer to expand appropriately, secondarily causing collapse of the underlying labyrinth layer. Additionally, we identify a population of proliferating Blimp1(+) diploid cells present within the spongiotrophoblast layer. Lineage tracing experiments exploiting a novel Prdm1.Cre-LacZ allele demonstrate that these Blimp1(+) cells give rise to the mature SpA-TGCs, canal TGCs, and glycogen trophoblasts. In sum, the transcriptional repressor Blimp1/Prdm1 is required for terminal differentiation of SpA-TGCs and defines a lineage-restricted progenitor cell population contributing to placental growth and morphogenesis.

Citing Articles

The zinc-finger transcription factor Blimp1/Prdm1 is required for uterine remodelling and repair in the mouse.

Xypolita M, Goolam M, Bikoff E, Robertson E, Mould A Nat Commun. 2025; 16(1):1220.

PMID: 39890816 PMC: 11785775. DOI: 10.1038/s41467-025-56511-8.

Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells.

Zhang X, Sun L iScience. 2025; 27(12):111484.

PMID: 39759022 PMC: 11699622. DOI: 10.1016/j.isci.2024.111484.

A spatiotemporal transcriptomic atlas of mouse placentation.

Wu Y, Su K, Zhang Y, Liang L, Wang F, Chen S Cell Discov. 2024; 10(1):110.

PMID: 39438452 PMC: 11496649. DOI: 10.1038/s41421-024-00740-6.

IL-27/Blimp-1 axis regulates the differentiation and function of Tim-3+ Tregs during early pregnancy.

Zhao S, Hu X, Lin X, Zhang Y, Wang J, Wang H JCI Insight. 2024; 9(16).

PMID: 39171524 PMC: 11343602. DOI: 10.1172/jci.insight.179233.

Conditionally mutant animal model for investigating the invasive trophoblast cell lineage.

Iqbal K, Dominguez E, Nixon B, Moreno-Irusta A, Crnkovich B, Scott R Development. 2023; 151(2).

PMID: 38112206 PMC: 10820817. DOI: 10.1242/dev.202239.

References

Vincent S, Dunn N, Sciammas R, Shapiro-Shalef M, Davis M, Calame K . The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development. 2005; 132(6):1315-25. DOI: 10.1242/dev.01711. View

Moffett A, Loke C . Immunology of placentation in eutherian mammals. Nat Rev Immunol. 2006; 6(8):584-94. DOI: 10.1038/nri1897. View

Smith M, Maurin M, Cho H, Becknell B, Freud A, Yu J . PRDM1/Blimp-1 controls effector cytokine production in human NK cells. J Immunol. 2010; 185(10):6058-67. PMC: 3864810. DOI: 10.4049/jimmunol.1001682. View

Tanaka S, Kunath T, Hadjantonakis A, Nagy A, Rossant J . Promotion of trophoblast stem cell proliferation by FGF4. Science. 1998; 282(5396):2072-5. DOI: 10.1126/science.282.5396.2072. View

Welsh R . Blimp hovers over T cell immunity. Immunity. 2009; 31(2):178-80. PMC: 3220184. DOI: 10.1016/j.immuni.2009.08.005. View

Kallies A, Nutt S . Terminal differentiation of lymphocytes depends on Blimp-1. Curr Opin Immunol. 2007; 19(2):156-62. DOI: 10.1016/j.coi.2007.01.003. View

Ben-Haim N, Lu C, Guzman-Ayala M, Pescatore L, Mesnard D, Bischofberger M . The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4. Dev Cell. 2006; 11(3):313-23. DOI: 10.1016/j.devcel.2006.07.005. View

Simmons D, Cross J . Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Dev Biol. 2005; 284(1):12-24. DOI: 10.1016/j.ydbio.2005.05.010. View

Robertson E, Charatsi I, Joyner C, Koonce C, Morgan M, Islam A . Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice. Development. 2007; 134(24):4335-45. PMC: 7116377. DOI: 10.1242/dev.012047. View

10.

Bouillot S, Rampon C, Tillet E, Huber P . Tracing the glycogen cells with protocadherin 12 during mouse placenta development. Placenta. 2005; 27(8):882-8. DOI: 10.1016/j.placenta.2005.09.009. View

11.

Tanaka M, Gertsenstein M, Rossant J, Nagy A . Mash2 acts cell autonomously in mouse spongiotrophoblast development. Dev Biol. 1997; 190(1):55-65. DOI: 10.1006/dbio.1997.8685. View

12.

Morgan M, Magnusdottir E, Kuo T, Tunyaplin C, Harper J, Arnold S . Blimp-1/Prdm1 alternative promoter usage during mouse development and plasma cell differentiation. Mol Cell Biol. 2009; 29(21):5813-27. PMC: 2772737. DOI: 10.1128/MCB.00670-09. View

13.

Constam D, Robertson E . SPC4/PACE4 regulates a TGFbeta signaling network during axis formation. Genes Dev. 2000; 14(9):1146-55. PMC: 316583. View

14.

Tesser R, Andrade Scherholz P, do Nascimento L, Katz S . Trophoblast glycogen cells differentiate early in the mouse ectoplacental cone: putative role during placentation. Histochem Cell Biol. 2010; 134(1):83-92. DOI: 10.1007/s00418-010-0714-x. View

15.

Navankasattusas S, Whitehead K, Suli A, Sorensen L, Lim A, Zhao J . The netrin receptor UNC5B promotes angiogenesis in specific vascular beds. Development. 2008; 135(4):659-67. PMC: 2612632. DOI: 10.1242/dev.013623. View

16.

Brown L, Alawoki M, Crawford M, Reida T, Sears A, Torma T . Lipocalin-7 is a matricellular regulator of angiogenesis. PLoS One. 2010; 5(11):e13905. PMC: 2976702. DOI: 10.1371/journal.pone.0013905. View

17.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

18.

Adamson S, Lu Y, Whiteley K, Holmyard D, Hemberger M, Pfarrer C . Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev Biol. 2002; 250(2):358-73. DOI: 10.1016/s0012-1606(02)90773-6. View

19.

Nutt S, Fairfax K, Kallies A . BLIMP1 guides the fate of effector B and T cells. Nat Rev Immunol. 2007; 7(12):923-7. DOI: 10.1038/nri2204. View

20.

Shimshek D, Kim J, Hubner M, Spergel D, Buchholz F, Casanova E . Codon-improved Cre recombinase (iCre) expression in the mouse. Genesis. 2002; 32(1):19-26. DOI: 10.1002/gene.10023. View