Open Access
Epigenetic memory in induced pluripotent stem cells
Kibem Kim,Akiko Doi,Bo Wen,K. Ng,Rui Zhao,Patrick Cahan,Jonghwan Kim,Martin J. Aryee,Hong Ji,Lauren I.R. Ehrlich,Lauren I.R. Ehrlich,A. Yabuuchi,A. Takeuchi,K. C. Cunniff,H. Hongguang,Shannon McKinney-Freeman,Olaia Naveiras,T. J. Yoon,T. J. Yoon,Rafael A. Irizarry,Namyoung Jung,Jun Seita,Jacob H. Hanna,Peter Murakami,Rudolf Jaenisch,Ralph Weissleder,Stuart H. Orkin,Irving L. Weissman,Andrew P. Feinberg,George Q. Daley +29 more
TLDR
The authors showed that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbor residual DNA methylation signatures characteristic of their somatic tissue of origin.Abstract:
Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.read more
Citations
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Journal ArticleDOI
Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells
Ryan Lister,Mattia Pelizzola,Yasuyuki S. Kida,R. David Hawkins,Joseph R. Nery,Gary C. Hon,Jessica Antosiewicz-Bourget,Jessica Antosiewicz-Bourget,Ronan C. O'Malley,Rosa Castanon,Sarit Klugman,Michael Downes,Ruth T. Yu,Ron Stewart,Ron Stewart,Bing Ren,Bing Ren,James A. Thomson,Ronald M. Evans,Joseph R. Ecker +19 more
TL;DR: The first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells are reported.
Book
Immunogenicity of Induced Pluripotent Stem Cells
TL;DR: Findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients.
Journal ArticleDOI
Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells
Jose M. Polo,Susanna Liu,Maria E. Figueroa,Warakorn Kulalert,Sarah Eminli,Kah Yong Tan,Effie Apostolou,Matthias Stadtfeld,Yushan Li,Toshihiro Shioda,Sridaran Natesan,Amy J. Wagers,Ari Melnick,Todd Evans,Konrad Hochedlinger +14 more
TL;DR: It is shown that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns, and it is demonstrated that cellular origin influences the in vitro differentiation potentials of iPSC into embryoid bodies and different hematopsic cell types.
Journal ArticleDOI
Control of the Embryonic Stem Cell State
TL;DR: This work has provided insights into the transcriptional control of embryonic stem cell state, including the regulatory circuitry underlying pluripotency and uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease.
Journal ArticleDOI
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.
Patricio Godoy,Nicola J. Hewitt,Ute Albrecht,Melvin E. Andersen,Nariman Ansari,Sudin Bhattacharya,Johannes G. Bode,Jennifer Bolleyn,Christoph Borner,J Böttger,Albert Braeuning,Robert A. Budinsky,Britta Burkhardt,Neil R. Cameron,Giovanni Camussi,Chong Su Cho,Yun Jaie Choi,J. Craig Rowlands,Uta Dahmen,Georg Damm,Olaf Dirsch,María Teresa Donato,Jian Dong,Steven Dooley,Dirk Drasdo,Dirk Drasdo,Dirk Drasdo,Rowena Eakins,Karine Sá Ferreira,Valentina Fonsato,Joanna Fraczek,Rolf Gebhardt,Andrew Gibson,Matthias Glanemann,Christopher E. Goldring,María José Gómez-Lechón,Geny M. M. Groothuis,Lena Gustavsson,Christelle Guyot,David Hallifax,Seddik Hammad,Adam S. Hayward,Dieter Häussinger,Claus Hellerbrand,Philip Hewitt,Stefan Hoehme,Hermann-Georg Holzhütter,J. Brian Houston,Jens Hrach,Kiyomi Ito,Hartmut Jaeschke,Verena Keitel,Jens M. Kelm,B. Kevin Park,Claus Kordes,Gerd A. Kullak-Ublick,Edward L. LeCluyse,Peng Lu,Jennifer Luebke-Wheeler,Anna Lutz,Daniel J. Maltman,Madlen Matz-Soja,Patrick D. McMullen,Irmgard Merfort,Simon Messner,Christoph Meyer,Jessica Mwinyi,Dean J. Naisbitt,Andreas K. Nussler,Peter Olinga,Francesco Pampaloni,Jingbo Pi,Linda J. Pluta,Stefan Przyborski,Anup Ramachandran,Vera Rogiers,Cliff Rowe,Celine Schelcher,Kathrin Schmich,Michael Schwarz,Bijay Singh,Ernst H. K. Stelzer,Bruno Stieger,Regina Stöber,Yuichi Sugiyama,Ciro Tetta,Wolfgang E. Thasler,Tamara Vanhaecke,Mathieu Vinken,Thomas S. Weiss,Agata Widera,Courtney G. Woods,Jinghai James Xu,Kathy Yarborough,Jan G. Hengstler +94 more
TL;DR: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes.
References
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Journal ArticleDOI
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TL;DR: The results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Journal ArticleDOI
The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
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