Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

被引：15

作者：

Naama, Moriyah ^{[1
]}

Rahamim, Moran ^{[1
]}

Zayat, Valery ^{[2
]}

Sebban, Shulamit ^{[1
]}

Radwan, Ahmed ^{[1
]}

Orzech, Dana ^{[1
]}

Lasry, Rachel ^{[1
]}

Ifrah, Annael ^{[1
]}

Jaber, Mohammad ^{[1
]}

Sabag, Ofra ^{[1
]}

Yassen, Hazar ^{[1
]}

Khatib, Areej ^{[1
]}

Epsztejn-Litman, Silvina ^{[3
,4
]}

Novoselsky-Persky, Michal ^{[5
]}

Makedonski, Kirill ^{[1
]}

Deri, Noy ^{[1
]}

Goldman-Wohl, Debra ^{[5
]}

Cedar, Howard ^{[1
]}

Yagel, Simcha ^{[5
]}

Eiges, Rachel ^{[3
,4
]}

Buganim, Yosef ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, IL-91120 Jerusalem, Israel

[2] Polish Acad Sci, Mossakowski Med Res Inst, Dept Stem Cell Bioengn, PL-02106 Warsaw, Poland

[3] Shaare Zedek Med Ctr, Inst Med Genet, Stem Cell Res Lab, IL-91031 Jerusalem, Israel

[4] Hebrew Univ Jerusalem, Sch Med, IL-91120 Jerusalem, Israel

[5] Hadassah Hebrew Univ, Dept Obstet & Gynecol, Magda & Richard Hoffman Lab Human Placental Res, Med Ctr, Jerusalem, Israel

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

RNA-SEQ REVEALS; SELF-RENEWAL; BIOCONDUCTOR PACKAGE; GENE-EXPRESSION; DIFFERENTIATION; TRANSCRIPTION; OCT4; TROPHECTODERM; MECHANISMS; CHROMATIN;

D O I：

10.1038/s41467-023-39104-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human trophoblast stem cells (hTSCs) can be derived from embryonic stem cells (hESCs) or be induced from somatic cells by OCT4, SOX2, KLF4 and MYC (OSKM). Here we explore whether the hTSC state can be induced independently of pluripotency, and what are the mechanisms underlying its acquisition. We identify GATA3, OCT4, KLF4 and MYC (GOKM) as a combination of factors that can generate functional hiTSCs from fibroblasts. Transcriptomic analysis of stable GOKM- and OSKM-hiTSCs reveals 94 hTSC-specific genes that are aberrant specifically in OSKM-derived hiTSCs. Through time-course-RNA-seq analysis, H3K4me2 deposition and chromatin accessibility, we demonstrate that GOKM exert greater chromatin opening activity than OSKM. While GOKM primarily target hTSC-specific loci, OSKM mainly induce the hTSC state via targeting hESC and hTSC shared loci. Finally, we show that GOKM efficiently generate hiTSCs from fibroblasts that harbor knockout for pluripotency genes, further emphasizing that pluripotency is dispensable for hTSC state acquisition.

引用

页数：22

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