Cellular population dynamics shape the route to human pluripotency

Francesco Panariello, Onelia Gagliano, Camilla Luni, Antonio Grimaldi, Silvia Angiolillo, Wei Qin, Anna Manfredi, Patrizia Annunziata, Shaked Slovin, Lorenzo Vaccaro, Sara Riccardo, Valentina Bouche, Manuela Dionisi, Marcello Salvi, Sebastian Martewicz, Manli Hu, Meihua Cui, Hannah Stuart, Cecilia Laterza, Giacomo Baruzzo, Geoffrey Schiebinger, Barbara Camillo, Davide Cacchiarelli () and Nicola Elvassore ()
Additional contact information
Francesco Panariello: Armenise/Harvard Laboratory of Integrative Genomics
Onelia Gagliano: University of Padova
Camilla Luni: ShanghaiTech University
Antonio Grimaldi: Armenise/Harvard Laboratory of Integrative Genomics
Silvia Angiolillo: University of Padova
Wei Qin: University of Padova
Anna Manfredi: Armenise/Harvard Laboratory of Integrative Genomics
Patrizia Annunziata: Armenise/Harvard Laboratory of Integrative Genomics
Shaked Slovin: Armenise/Harvard Laboratory of Integrative Genomics
Lorenzo Vaccaro: Armenise/Harvard Laboratory of Integrative Genomics
Sara Riccardo: Armenise/Harvard Laboratory of Integrative Genomics
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
Cecilia Laterza: University of Padova
Giacomo Baruzzo: University of Padova
Geoffrey Schiebinger: University of British Columbia
Barbara Camillo: University of Padova
Davide Cacchiarelli: Armenise/Harvard Laboratory of Integrative Genomics
Nicola Elvassore: University of Padova

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37270-w

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