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
N1 - Publisher Copyright:
© 2023, The Author(s).
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
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C2 - 37291192
AN - SCOPUS:85161338642
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3359
ER -