Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells

被引：132

作者：

Castel, Gael ^{[1
]}

Meistermann, Dimitri ^{[1
,2
]}

Bretin, Betty ^{[1
]}

Firmin, Julie ^{[1
,3
]}

Blin, Justine ^{[4
]}

Loubersac, Sophie ^{[3
]}

Bruneau, Alexandre ^{[1
]}

Chevolleau, Simon ^{[1
]}

Kilens, Stephanie ^{[1
]}

Chariau, Caroline ^{[5
]}

Gaignerie, Anne ^{[5
]}

Francheteau, Quentin ^{[5
]}

Kagawa, Harunobu ^{[6
]}

Charpentier, Eric ^{[5
]}

Flippe, Lea ^{[1
]}

Francois--Campion, Valentin ^{[1
]}

Haider, Sandra ^{[7
]}

Dietrich, Bianca ^{[7
]}

Knoefler, Martin ^{[7
]}

Arima, Takahiro ^{[8
]}

Bourdon, Jeremie ^{[2
]}

Rivron, Nicolas ^{[6
]}

Masson, Damien ^{[4
,9
]}

Fournier, Thierry ^{[10
]}

Okae, Hiroaki ^{[8
]}

Freour, Thomas ^{[1
,3
]}

David, Laurent ^{[1
,5
]}

机构：

[1] Univ Nantes, Ctr Rech Transplantat & Immunol, ITUN, INSERM,UMR 1064,CHU Nantes, F-44000 Nantes, France

[2] Univ Nantes, CNRS, LS2N, Nantes, France

[3] CHU Nantes, Serv Biol Reprod, Nantes, France

[4] CHU Nantes, Lab Clin Biochem, Nantes, France

[5] Univ Nantes, FED 4203, SFR Sante, CHU Nantes,INSERM UMS 016,CNRS,UMS 3556, Nantes, France

[6] Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria

[7] Med Univ Vienna, Dept Obstet & Gynaecol, Reprod Biol Unit, Wahringer Gurtel 18-20,5Q, A-1090 Vienna, Austria

[8] Tohoku Univ, Environm & Genome Res Ctr, Dept Informat Genet, Grad Sch Med, Sendai, Miyagi 9808575, Japan

[9] Univ Nantes, U1235, INSERM, Nantes, France

[10] Univ Paris, 3PHM, INSERM, UMR S 1139, F-75006 Paris, France

来源：

CELL REPORTS | 2020年 / 33卷 / 08期

关键词：

cell fate conversion; extended pluripotent stem cells; human induced trophoblast stem cells; human peri-implantation embryo; human placenta; induced pluripotent stem cells; naive pluripotent stem cells; OSKM; somatic cell reprogramming; trophoblast stem cells;

D O I：

10.1016/j.celrep.2020.108419

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access to human embryos and first-trimester placentas is limited, thus preventing the establishment of hTSCs from diverse genetic backgrounds associated with placental disorders, Here, we show that hTSCs can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (1) somatic cell reprogramming of adult fibroblasts with OCT4, SOX2, KLF4, MYC (OSKM) and (2) cell fate conversion of naive and extended pluripotent stem cells. The resulting induced/converted hTSCs recapitulated hallmarks of hTSCs including long-term self-renewal, expression of specific transcription factors, transcriptomic signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSCs and show that these cells resemble day 8 cytotrophoblasts. Altogether, hTSC lines of diverse genetic origins open the possibility to model both placental development and diseases in a dish.

引用

页数：21

共 53 条

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