Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

Moriyah Naama; Moran Rahamim; Valery Zayat; Shulamit Sebban; Ahmed Radwan; Dana Orzech; Rachel Lasry; Annael Ifrah; Mohammad Jaber; Ofra Sabag; Hazar Yassen; Areej Khatib; Silvina Epsztejn-Litman; Michal Novoselsky-Persky; Kirill Makedonski; Noy Deri; Debra Goldman-Wohl; Howard Cedar; Simcha Yagel; Rachel Eiges; Yosef Buganim

doi:10.1038/s41467-023-39104-1

Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

Moriyah Naama, Moran Rahamim, Valery Zayat, Shulamit Sebban, Ahmed Radwan, Dana Orzech, Rachel Lasry, Annael Ifrah, Mohammad Jaber, Ofra Sabag, Hazar Yassen, Areej Khatib, Silvina Epsztejn-Litman, Michal Novoselsky-Persky, Kirill Makedonski, Noy Deri, Debra Goldman-Wohl, Howard Cedar, Simcha Yagel, Rachel EigesYosef Buganim

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	3359
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-39104-1
State	Published - 8 Jun 2023

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Naama, M., Rahamim, M., Zayat, V., Sebban, S., Radwan, A., Orzech, D., Lasry, R., Ifrah, A., Jaber, M., Sabag, O., Yassen, H., Khatib, A., Epsztejn-Litman, S., Novoselsky-Persky, M., Makedonski, K., Deri, N., Goldman-Wohl, D., Cedar, H., Yagel, S., ... Buganim, Y. (2023). Pluripotency-independent induction of human trophoblast stem cells from fibroblasts. Nature Communications, 14(1), Article 3359. https://doi.org/10.1038/s41467-023-39104-1

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title = "Pluripotency-independent induction of human trophoblast stem cells from fibroblasts",

abstract = "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.",

author = "Moriyah Naama and Moran Rahamim and Valery Zayat and Shulamit Sebban and Ahmed Radwan and Dana Orzech and Rachel Lasry and Annael Ifrah and Mohammad Jaber and Ofra Sabag and Hazar Yassen and Areej Khatib and Silvina Epsztejn-Litman and Michal Novoselsky-Persky and Kirill Makedonski and Noy Deri and Debra Goldman-Wohl and Howard Cedar and Simcha Yagel and Rachel Eiges and Yosef Buganim",

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year = "2023",

month = jun,

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doi = "10.1038/s41467-023-39104-1",

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Naama, M, Rahamim, M, Zayat, V, Sebban, S, Radwan, A, Orzech, D, Lasry, R, Ifrah, A, Jaber, M, Sabag, O, Yassen, H, Khatib, A, Epsztejn-Litman, S, Novoselsky-Persky, M, Makedonski, K, Deri, N, Goldman-Wohl, D, Cedar, H, Yagel, S, Eiges, R & Buganim, Y 2023, 'Pluripotency-independent induction of human trophoblast stem cells from fibroblasts', Nature Communications, vol. 14, no. 1, 3359. https://doi.org/10.1038/s41467-023-39104-1

TY - JOUR

T1 - Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

AU - Naama, Moriyah

AU - Rahamim, Moran

AU - Zayat, Valery

AU - Sebban, Shulamit

AU - Radwan, Ahmed

AU - Orzech, Dana

AU - Lasry, Rachel

AU - Ifrah, Annael

AU - Jaber, Mohammad

AU - Sabag, Ofra

AU - Yassen, Hazar

AU - Khatib, Areej

AU - Epsztejn-Litman, Silvina

AU - Novoselsky-Persky, Michal

AU - Makedonski, Kirill

AU - Deri, Noy

AU - Goldman-Wohl, Debra

AU - Cedar, Howard

AU - Yagel, Simcha

AU - Eiges, Rachel

AU - Buganim, Yosef

PY - 2023/6/8

Y1 - 2023/6/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85161338642&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-39104-1

DO - 10.1038/s41467-023-39104-1

M3 - مقالة

C2 - 37291192

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3359

ER -

Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

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