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Cellular population dynamics shape the route to human pluripotency

Author

Listed:
  • Francesco Panariello

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Onelia Gagliano

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM)
    University College London)

  • Camilla Luni

    (ShanghaiTech University
    University of Bologna)

  • Antonio Grimaldi

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Silvia Angiolillo

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM))

  • Wei Qin

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM)
    ShanghaiTech University)

  • Anna Manfredi

    (Armenise/Harvard Laboratory of Integrative Genomics
    NEGEDIA (Next Generation Diagnostic srl))

  • Patrizia Annunziata

    (Armenise/Harvard Laboratory of Integrative Genomics
    NEGEDIA (Next Generation Diagnostic srl))

  • Shaked Slovin

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Lorenzo Vaccaro

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Sara Riccardo

    (Armenise/Harvard Laboratory of Integrative Genomics
    NEGEDIA (Next Generation Diagnostic srl))

  • Valentina Bouche

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Manuela Dionisi

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Marcello Salvi

    (Armenise/Harvard Laboratory of Integrative Genomics)

  • Sebastian Martewicz

    (ShanghaiTech University)

  • Manli Hu

    (ShanghaiTech University)

  • Meihua Cui

    (ShanghaiTech University)

  • Hannah Stuart

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM))

  • Cecilia Laterza

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM))

  • Giacomo Baruzzo

    (University of Padova)

  • Geoffrey Schiebinger

    (University of British Columbia)

  • Barbara Camillo

    (University of Padova
    University of Padova
    University of Padova)

  • Davide Cacchiarelli

    (Armenise/Harvard Laboratory of Integrative Genomics
    University of Naples “Federico II”
    University of Naples “Federico II”)

  • Nicola Elvassore

    (University of Padova
    Veneto Institute of Molecular Medicine (VIMM)
    University College London
    ShanghaiTech University)

Abstract

Human cellular reprogramming to induced pluripotency is still an inefficient process, which has hindered studying the role of critical intermediate stages. Here we take advantage of high efficiency reprogramming in microfluidics and temporal multi-omics to identify and resolve distinct sub-populations and their interactions. We perform secretome analysis and single-cell transcriptomics to show functional extrinsic pathways of protein communication between reprogramming sub-populations and the re-shaping of a permissive extracellular environment. We pinpoint the HGF/MET/STAT3 axis as a potent enhancer of reprogramming, which acts via HGF accumulation within the confined system of microfluidics, and in conventional dishes needs to be supplied exogenously to enhance efficiency. Our data suggest that human cellular reprogramming is a transcription factor-driven process that it is deeply dependent on extracellular context and cell population determinants.

Suggested Citation

  • Francesco Panariello & Onelia Gagliano & Camilla Luni & Antonio Grimaldi & Silvia Angiolillo & Wei Qin & Anna Manfredi & Patrizia Annunziata & Shaked Slovin & Lorenzo Vaccaro & Sara Riccardo & Valenti, 2023. "Cellular population dynamics shape the route to human pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37270-w
    DOI: 10.1038/s41467-023-37270-w
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