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Pluripotency-independent induction of human trophoblast stem cells from fibroblasts

Author

Listed:
  • Moriyah Naama

    (The Hebrew University-Hadassah Medical School)

  • Moran Rahamim

    (The Hebrew University-Hadassah Medical School)

  • Valery Zayat

    (Polish Academy of Sciences)

  • Shulamit Sebban

    (The Hebrew University-Hadassah Medical School)

  • Ahmed Radwan

    (The Hebrew University-Hadassah Medical School)

  • Dana Orzech

    (The Hebrew University-Hadassah Medical School)

  • Rachel Lasry

    (The Hebrew University-Hadassah Medical School)

  • Annael Ifrah

    (The Hebrew University-Hadassah Medical School)

  • Mohammad Jaber

    (The Hebrew University-Hadassah Medical School)

  • Ofra Sabag

    (The Hebrew University-Hadassah Medical School)

  • Hazar Yassen

    (The Hebrew University-Hadassah Medical School)

  • Areej Khatib

    (The Hebrew University-Hadassah Medical School)

  • Silvina Epsztejn-Litman

    (Medical Genetics Institute, Shaare Zedek Medical Center
    The Hebrew University School of Medicine)

  • Michal Novoselsky-Persky

    (Hadassah-Hebrew University Medical Center)

  • Kirill Makedonski

    (The Hebrew University-Hadassah Medical School)

  • Noy Deri

    (The Hebrew University-Hadassah Medical School)

  • Debra Goldman-Wohl

    (Hadassah-Hebrew University Medical Center)

  • Howard Cedar

    (The Hebrew University-Hadassah Medical School)

  • Simcha Yagel

    (Hadassah-Hebrew University Medical Center)

  • Rachel Eiges

    (Medical Genetics Institute, Shaare Zedek Medical Center
    The Hebrew University School of Medicine)

  • Yosef Buganim

    (The Hebrew University-Hadassah Medical School)

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.

Suggested Citation

  • 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, 2023. "Pluripotency-independent induction of human trophoblast stem cells from fibroblasts," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39104-1
    DOI: 10.1038/s41467-023-39104-1
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    References listed on IDEAS

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    1. Francesco Cambuli & Alexander Murray & Wendy Dean & Dominika Dudzinska & Felix Krueger & Simon Andrews & Claire E. Senner & Simon J. Cook & Myriam Hemberger, 2014. "Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    2. Paulina A. Latos & Angela Goncalves & David Oxley & Hisham Mohammed & Ernest Turro & Myriam Hemberger, 2015. "Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
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    7. Mohammad Jaber & Ahmed Radwan & Netanel Loyfer & Mufeed Abdeen & Shulamit Sebban & Areej Khatib & Hazar Yassen & Thorsten Kolb & Marc Zapatka & Kirill Makedonski & Aurelie Ernst & Tommy Kaplan & Yosef, 2022. "Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
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    Cited by:

    1. Timothy D. Arthur & Jennifer P. Nguyen & Agnieszka D’Antonio-Chronowska & Hiroko Matsui & Nayara S. Silva & Isaac N. Joshua & André D. Luchessi & William W. Young Greenwald & Matteo D’Antonio & Martin, 2024. "Complex regulatory networks influence pluripotent cell state transitions in human iPSCs," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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