Production of hepatocyte-like cells from human pluripotent stem cells
Nicholas R.F. Hannan,Charis-Patricia Segeritz,Thomas Touboul,Ludovic Vallier,Ludovic Vallier +4 more
Reads0
Chats0
TLDR
A 25-d protocol to direct the differentiation of human pluripotent stem cells into a near-homogenous population of hepatocyte-like cells and expresses genes in a chronological manner similar to that described during in vivo hepatic development is described.Abstract:
Large-scale production of hepatocytes from a variety of genetic backgrounds would be beneficial for drug screening and to provide a source of cells to be used as a substitute for liver transplantation. However, fully functional primary hepatocytes remain difficult to expand in vitro, and circumventing this problem by using an alternative source of cells is desirable. Here we describe a 25-d protocol to direct the differentiation of human pluripotent stem cells into a near-homogenous population of hepatocyte-like cells. As cells progress through this protocol, they express genes in a chronological manner similar to that described during in vivo hepatic development. The protocol relies on culture systems devoid of serum, feeders or complex extracellular matrices, which enable molecular analyses without interference from unknown factors. This approach works efficiently with human embryonic stem cells and human induced pluripotent stem cells and was recently used to model liver diseases in vitro.read more
Citations
More filters
Journal ArticleDOI
Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation
Fotios Sampaziotis,Fotios Sampaziotis,Miguel Cardoso de Brito,Pedro Madrigal,Pedro Madrigal,Alessandro Bertero,Kourosh Saeb-Parsy,Filipa A.C. Soares,E. Schrumpf,E. Schrumpf,Espen Melum,Tom H. Karlsen,Tom H. Karlsen,J. Andrew Bradley,William Gelson,Susan E. Davies,Alastair Baker,Arthur Kaser,Graeme J.M. Alexander,Nicholas R.F. Hannan,Ludovic Vallier,Ludovic Vallier +21 more
TL;DR: An efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs) is presented, which will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.
Journal ArticleDOI
GDF15 mediates the effects of metformin on body weight and energy balance
Anthony P. Coll,Michael Chen,Pranali Taskar,Debra Rimmington,Satish Patel,John Tadross,Irene Cimino,Ming Yang,Paul Welsh,Sam Virtue,Deborah A. Goldspink,Emily L. Miedzybrodzka,Adam R. Konopka,Raul Ruiz Esponda,Jeffrey T.-J. Huang,Y. C. Loraine Tung,Sergio Rodriguez-Cuenca,Rute A. Tomaz,Heather P. Harding,Audrey Melvin,Giles S.H. Yeo,David Preiss,Antonio Vidal-Puig,Ludovic Vallier,K. Sreekumaran Nair,Nicholas J. Wareham,David Ron,Fiona M. Gribble,Frank Reimann,Naveed Sattar,David B. Savage,Bernard B. Allan,Stephen O'Rahilly +32 more
TL;DR: It is shown—in two independent randomized controlled clinical trials—that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor.
Journal ArticleDOI
Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes
Melissa A. Baxter,Sarah L. Withey,Sean Harrison,Charis-Patricia Segeritz,Charis-Patricia Segeritz,Fang Zhang,Rebecca Atkinson-Dell,Cliff Rowe,Cliff Rowe,Dave T. Gerrard,Rowena Sison-Young,Roz Jenkins,Joanne Henry,Andrew Berry,Lisa Mohamet,Marie Best,Stephen W. Fenwick,Hassan Malik,Neil R. Kitteringham,Christopher E. Goldring,Karen Piper Hanley,Ludovic Vallier,Ludovic Vallier,Neil A. Hanley,Neil A. Hanley +24 more
TL;DR: In this article, the authors generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes, and found that HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype.
Journal ArticleDOI
Generation of lung organoids from human pluripotent stem cells in vitro.
Alyssa J. Miller,Briana R. Dye,Daysha Ferrer-Torres,David R. Hill,Arend W. Overeem,Lonnie D. Shea,Jason R. Spence +6 more
TL;DR: A protocol that recapitulates several of these milestones in order to differentiate human pluripotent stem cells (hPSCs) into ventral–anterior foregut spheroids and further into two distinct types of organoids: human lung organoids and bud tip progenitor organoids.
Journal ArticleDOI
Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells
Karl R. Koehler,Jing Nie,Emma Longworth-Mills,Xiao Ping Liu,Jiyoon Lee,Jeffrey R. Holt,Eri Hashino +6 more
TL;DR: A method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells and it is demonstrated that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells.
References
More filters
Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
Journal ArticleDOI
Embryonic Stem Cell Lines Derived from Human Blastocysts
James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Journal ArticleDOI
Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: This work generated induced pluripotent stem cells capable of germline transmission from murine somatic cells by transd, and demonstrated the ability of these cells to reprogram into patient-specific and disease-specific stem cells.
Journal ArticleDOI
Derivation of pluripotent epiblast stem cells from mammalian embryos
I. Gabrielle M. Brons,Lucy E. Smithers,Matthew Trotter,Peter J. Rugg-Gunn,Bowen Sun,Susana M. Chuva de Sousa Lopes,Sarah K. Howlett,Amanda Clarkson,Lars Ährlund-Richter,Roger A. Pedersen,Ludovic Vallier +10 more
TL;DR: It is shown that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells.
Journal ArticleDOI
Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells
Kosuke Yusa,S. Tamir Rashid,Helene Strick-Marchand,Helene Strick-Marchand,Ignacio Varela,Pei-Qi Liu,David Paschon,Elena Miranda,Elena Miranda,Adriana Ordóñez,Nicholas R.F. Hannan,Foad J. Rouhani,Foad J. Rouhani,Sylvie Darche,Sylvie Darche,Graeme J.M. Alexander,Stefan J. Marciniak,Noemi Fusaki,Mamoru Hasegawa,Michael C. Holmes,James P. Di Santo,James P. Di Santo,David A. Lomas,Allan Bradley,Ludovic Vallier +24 more
TL;DR: This work shows that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation in the α1-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α1