4.8 Article

Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics

期刊

NATURE CELL BIOLOGY
卷 21, 期 2, 页码 275-+

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-018-0254-5

关键词

-

资金

  1. Giovanni Armenise-Harvard Foundation
  2. Telethon Foundation [GGP15275, TCP13013]
  3. Rita Levi Montalcini programme from MIUR
  4. ERC Starting Grant (CellKarma)
  5. Italian Association for Cancer Research [IG17185]
  6. BMBF eMed grant [01ZX1504]
  7. Max Planck Society
  8. University of Padova (TRANSAC)
  9. University of Padova (PRAT)
  10. CaRiPaRo Foundation
  11. Oak Foundation Award [W1095/OCAY-14-19]
  12. NIHR GOSH BRC
  13. ERC Starting Grant (MetEpiStem)

向作者/读者索取更多资源

Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors OCT4 (also known as POU5F1), SOX2, KLF4 and cMYC (OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with NANOG for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemistry & Molecular Biology

A Porous Gelatin Methacrylate-Based Material for 3D Cell-Laden Constructs

Lorenzo Bova, Federico Maggiotto, Sara Micheli, Monica Giomo, Paolo Sgarbossa, Onelia Gagliano, Dario Falcone, Elisa Cimetta

Summary: This study blends GelMA with PLU to modify the hydrogel's internal porosity and achieve the customization of cell constructs. The blended materials form stable hydrogels when bioprinted in complex structures, and the embedded cells maintain high viability.

MACROMOLECULAR BIOSCIENCE (2023)

Article Genetics & Heredity

Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association

M. Cesana, L. Vaccaro, M. J. Larsen, M. Kibaek, L. Micale, S. Riccardo, P. Annunziata, C. Colantuono, L. Di Filippo, D. De Brasi, M. Castori, C. Fagerberg, F. Acquaviva, D. Cacchiarelli

Summary: This study applied integrated genomic approaches to identify a novel neuro-pathogenic role for the MAP4K4 gene by analyzing blood samples of two unrelated individuals with neurodevelopmental disorders. The study demonstrated the efficacy of exome and transcriptome sequencing in resolving undiagnosed cases.

HUMAN GENETICS (2023)

Article Oncology

A comprehensive investigation of histotype-specific microRNA and their variants in Stage I epithelial ovarian cancers

Angelo Velle, Chiara Pesenti, Tommaso Grassi, Luca Beltrame, Paolo Martini, Marta Jaconi, Federico Agostinis, Enrica Calura, Dionyssios Katsaros, Fulvio Borella, Robert Fruscio, Maurizio D'Incalci, Sergio Marchini, Chiara Romualdi

Summary: In this study, we investigated the expression of isomiRs in different histological subtypes of Stage I epithelial ovarian cancer (EOC) for the first time, aiming to gain new insights into their biological role in tumor growth and progression.

INTERNATIONAL JOURNAL OF CANCER (2023)

Article Multidisciplinary Sciences

Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle

Caterina Marchioretti, Giulia Zanetti, Marco Pirazzini, Gaia Gherardi, Leonardo Nogara, Roberta Andreotti, Paolo Martini, Lorenzo Marcucci, Marta Canato, Samir R. Nath, Emanuela Zuccaro, Mathilde Chivet, Cristina Mammucari, Marco Pacifici, Anna Raffaello, Rosario Rizzuto, Andrea Mattarei, Maria A. Desbats, Leonardo Salviati, Aram Megighian, Gianni Soraru, Elena Pegoraro, Elisa Belluzzi, Assunta Pozzuoli, Carlo Biz, Pietro Ruggieri, Chiara Romualdi, Andrew P. Lieberman, Gopal J. Babu, Marco Sandri, Bert Blaauw, Manuela Basso, Maria Pennuto

Summary: Marchioretti and colleagues demonstrate that there are reversible alterations in gene expression related to muscle contraction and mitochondrial respiration in the skeletal muscle of SBMA mice and patients. These alterations are accompanied by calcium accumulation inside the mitochondria, motor dysfunction, and late changes in muscle structure. The deregulation of expression of genes involved in excitation-contraction coupling (ECC) occurs with sexual maturity and androgen increase in the serum. Surgical castration and AR silencing alleviate the early and late pathological processes, indicating an androgen-dependent nature of these alterations.

NATURE COMMUNICATIONS (2023)

Article Cell Biology

Spatial compartmentalization of signaling imparts source-specific functions on secreted factors

Elena Groppa, Paolo Martini, Nima Derakhshan, Marine Theret, Morten Ritso, Lin Wei Tung, Yu Xin Wang, Hesham Soliman, Mark Stephen Hamer, Laura Stankiewicz, Christine Eisner, Le Neve Erwan, Chihkai Chang, Lin Yi, Jack H. Yuan, Sunny Kong, Curtis Weng, Josephine Adams, Lucas Chang, Anne Peng, Helen M. Blau, Chiara Romualdi, Fabio M. V. Rossi

Summary: Efficient regeneration requires coordination between multiple cell types. This study analyzes the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells to understand the intercellular networks involved in regeneration. The findings identify VEGFA-driven endothelial engagement as a key differentiating feature in successful and failed regeneration models. Additionally, the study reveals that multiple cell types simultaneously produce most secreted signals, including VEGFA. Deleting VEGFA from stromal and myogenic progenitors shows that spatial compartmentalization of signaling plays a crucial role in intercellular communication networks.

CELL REPORTS (2023)

Article Biology

Requirement for STAT3 and its target, TFCP2L1, in self-renewal of naive pluripotent stem cells in vivo and in vitro

Sophie Kraunsoe, Takuya Azami, Yihan Pei, Graziano Martello, Kenneth Jones, Thorsten Boroviak, Jennifer Nichols

Summary: We investigated the roles of STAT3 and TFCP2L1 in maintaining naive pluripotency and found that their protein levels decline during blastocyst expansion but increase in the embryonic region after diapause induction. Embryos lacking STAT3 or TFCP2L1 showed catastrophic loss of the inner cell mass during diapause, indicating additional signals are required for sustaining pluripotency. Blocking MEK/ERK signaling allowed efficient derivation of embryonic stem cells from STAT3 null embryos, highlighting an unknown role of TFCP2L1 in the transition to embryonic stem cells in vitro.

BIOLOGY OPEN (2023)

Article Biochemistry & Molecular Biology

Chemical conversion of human conventional PSCs to TSCs following transient naive gene activation

Irene Zorzan, Riccardo Massimiliano Betto, Giada Rossignoli, Mattia Arboit, Andrea Drusin, Clelia Corridori, Paolo Martini, Graziano Martello

Summary: In human embryos, naive pluripotent cells of the inner cell mass (ICM) generate different cell lineages, including trophoblast cells. In vitro, chemical resetting can convert conventional pluripotent stem cells into naive pluripotent stem cells, which have the potential to efficiently generate trophoblast stem cells. This method can be used to study cell fate transitions and model placental disorders.

EMBO REPORTS (2023)

Article Cell Biology

Esrrb guides naive pluripotent cells through the formative transcriptional programme

Elena Carbognin, Valentina Carlini, Francesco Panariello, Martina Chieregato, Elena Guerzoni, Davide Benvegnu, Valentina Perrera, Cristina Malucelli, Marcella Cesana, Antonio Grimaldi, Margherita Mutarelli, Annamaria Carissimo, Eitan Tannenbaum, Hillel Kugler, Jamie A. Hackett, Davide Cacchiarelli, Graziano Martello

Summary: Carbognin et al. found that ESRRB is essential for the activation of formative genes during the transition of naive embryonic stem cells to a formative state. Inactivation of Esrrb leads to abnormal expression of specific markers and impairs the ability of the cells to self-organize. ESRRB occupies key formative genes in both naive cells and throughout the formative state, kickstarting the formative transition and enabling unbiased multi-lineage differentiation.

NATURE CELL BIOLOGY (2023)

Article Biochemistry & Molecular Biology

EGR1 drives cell proliferation by directly stimulating TFEB transcription in response to starvation

Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Susanna Ambrosio, Rossella De Cegli, Margherita Mutarelli, Lorenzo Vaccaro, Micheal J. Ziller, Davide Cacchiarelli, Diego L. Medina, Andrea Ballabio

Summary: The transcription factor EB (TFEB) is an important regulator of lysosomal biogenesis and autophagy and plays a major role in cancer-associated diseases. The nutrient-sensitive kinase complex mTORC1 regulates TFEB at the posttranslational level, but the regulation of TFEB transcription is not well understood. In this study, the immediate-early gene EGR1 was identified as a positive regulator of TFEB expression and its absence impaired TFEB-mediated transcriptional response to starvation. Inhibition of EGR1, either genetically or pharmacologically using the MEK1/2 inhibitor Trametinib, significantly reduced the proliferation of cells with constitutive activation of TFEB, including those from a patient with Birt-Hogg-Dube (BHD) syndrome. This suggests that targeting the EGR1-TFEB axis may be a potential therapeutic strategy for cancer-associated conditions with constitutive TFEB activation.

PLOS BIOLOGY (2023)

Article Genetics & Heredity

Transcriptional Profiling of Rat Prefrontal Cortex after Acute Inescapable Footshock Stress

Paolo Martini, Jessica Mingardi, Giulia Carini, Stefania Mattevi, Elona Ndoj, Luca La Via, Chiara Magri, Massimo Gennarelli, Isabella Russo, Maurizio Popoli, Laura Musazzi, Alessandro Barbon

Summary: Stress is a major risk factor for psychiatric disorders, and the response to stress involves the regulation of transcriptional programs. In this study, we analyzed the gene expression changes in the prefrontal cortex (PFC) of rats exposed to acute footshock stress. We found alterations in neuronal pathways, glia development, glia-neuron networking, and synaptic function. Furthermore, specific transcription factors were identified as potential master regulators of the acute stress response.
Article Biochemistry & Molecular Biology

TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression

Adrien Pasquier, Nunzia Pastore, Luca D'Orsi, Rita Colonna, Alessandra Esposito, Veronica Maffia, Rossella De Cegli, Margherita Mutarelli, Susanna Ambrosio, Gennaro Tufano, Antonio Grimaldi, Marcella Cesana, Davide Cacchiarelli, Nathalie Delalleau, Gennaro Napolitano, Andrea Ballabio

Summary: Pancreatic beta cells require precise nutrient-sensing mechanisms to control insulin production. Transcription factors TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. TFEB and TFE3 are activated by nutrient deprivation, resulting in suppression of insulin gene expression. Genetic manipulation of TFEB and TFE3 affects body weight and glucose tolerance in mice.

EMBO JOURNAL (2023)

Article Biochemical Research Methods

benchdamic: benchmarking of differential abundance methods for microbiome data

Matteo Calgaro, Chiara Romualdi, Davide Risso, Nicola Vitulo

Summary: This article presents benchdamic, a Bioconductor package for benchmarking methods for the identification of differentially abundant taxa.

BIOINFORMATICS (2023)

暂无数据