Rudolf Jaenisch

Whitehead Institute for Biomedical Research

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Document Type

Co-Authors

Konrad Hochedlinger

Harvard University

Styliani Markoulaki

Whitehead Institute for Biomedical Research

Richard A. Young

Whitehead Institute for Biomedical Research

Albert W. Cheng

Arizona State University

Frank Soldner

Research Network (United States)

Qing Gao

Chinese Academy of Medical Sciences & Peking Union Medical College

Jacob H. Hanna

Weizmann Institute of Science

Meelad M. Dawlaty

Albert Einstein College of Medicine

Caroline Beard

Whitehead Institute for Biomedical Research

Haoyi Wang

Qilu Hospital of Shandong University

Cooperative Institutions

Harvard University

594

Massachusetts Institute of Technology

565

Whitehead Institute for Biomedical Research

385

Howard Hughes Medical Institute

259

Broad Institute

188

Brigham and Women's Hospital

182

Massachusetts General Hospital

171

Dana-Farber Cancer Institute

162

Stanford University

136

Boston Children's Hospital

122

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ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable

Proceedings of the National Academy of Sciences (2006)

Tobias Brambrink Konrad Hochedlinger George W. Bell Rudolf Jaenisch

Reproductive cloning is uniformly rejected as a valid technology in humans because of the severely abnormal phenotypes seen in cloned animals. Gene expression aberrations observed in tissues of cloned animals have also raised concerns regarding the therapeutic application of “customized” embryonic stem (ES) cells derived by nuclear transplantation (NT) from a patient's somatic cells. Although previous experiments in mice have demonstrated that the developmental potential of ES cells derived from cloned blastocysts (NT-ES cells) is identical to that of ES cells derived from fertilized blastocysts, a systematic molecular characterization of NT-ES cell lines is lacking. To investigate whether transcriptional aberrations, similar to those observed in tissues of cloned mice, also occur in NT-ES cells, we have compared transcriptional profiles of 10 mouse NT- and fertilization-derived-ES cell lines. We report here that the ES cell lines derived from cloned and fertilized mouse blastocysts are indistinguishable based on their transcriptional profiles, consistent with their normal developmental potential. Our results indicate that, in contrast to embryonic and fetal development of clones, the process of NT-ES cell derivation rigorously selects for those immortal cells that have erased the “epigenetic memory” of the donor nucleus and, thus, become functionally equivalent. Our findings support the notion that ES cell lines derived from cloned or fertilized blastocysts have an identical therapeutic potential.

Cloning (programming)

Inner cell mass

10.1073/pnas.0510485103

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Citations (225)

Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations

Cell (2010)

Christopher J. Lengner Alexander A. Gimelbrant Jennifer A. Erwin Albert W. Cheng Matthew G. Guenther

XIST

Inner cell mass

10.1016/j.cell.2010.04.010

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Citations (399)

Recessive and dominant mutations in transgenic mice.

Rudolf Jaenisch Douglas A. Gray Tomoko Noda Hans Weiher

Source

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Citations (0)

Retrovirus-induced insertional mutation in Mov13 mice affects collagen I expression in a tissue-specific manner

Cell (1989)

Klaus Kratochwil Klaus von der Mark Edward J. Kollar Rudolf Jaenisch Katrin Mooslehner

Transcription

10.1016/0092-8674(89)90795-2

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Citations (111)

Metastable Pluripotent States in NOD-Mouse-Derived ESCs

Cell stem cell (2009)

Jacob H. Hanna Styliani Markoulaki Maisam Mitalipova Albert W. Cheng John P. Cassady

Epiblast

Reprogramming

KLF4

Inner cell mass

10.1016/j.stem.2009.04.015

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Citations (320)

A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells

Cell (2006)

B Bernstein Tarjei S. Mikkelsen Xiaohui Xie Michael Kamal Dana J. Huebert

Bivalent (engine)

Bivalent chromatin

Histone Methylation

10.1016/j.cell.2006.02.041

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Citations (5,161)

Reprogramming Efficiency Following Somatic Cell Nuclear Transfer Is Influenced by the Differentiation and Methylation State of the Donor Nucleus

Stem Cells (2006)

Robert Blelloch Zhongde Wang Alex Meissner Steven M. Pollard Austin Smith

Reprogramming of a differentiated cell nucleus by somatic cell nuclear transplantation is an inefficient process. Following nuclear transfer, the donor nucleus often fails to express early embryonic genes and establish a normal embryonic pattern of chromatin modifications. These defects correlate with the low number of cloned embryos able to produce embryonic stem cells or develop into adult animals. Here, we show that the differentiation and methylation state of the donor cell influence the efficiency of genomic reprogramming. First, neural stem cells, when used as donors for nuclear transplantation, produce embryonic stem cells at a higher efficiency than blastocysts derived from terminally differentiated neuronal donor cells, demonstrating a correlation between the state of differentiation and cloning efficiency. Second, using a hypomorphic allele of DNA methyltransferase‐1, we found that global hypomethylation of a differentiated cell genome improved cloning efficiency. Our results provide functional evidence that the differentiation and epigenetic state of the donor nucleus influences reprogramming efficiency.

Reprogramming

Cell potency

Cloning (programming)

10.1634/stemcells.2006-0050

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Citations (274)

Mechanisms and models of somatic cell reprogramming

Nature Reviews Genetics (2013)

Yosef Buganim Dina A. Faddah Rudolf Jaenisch

Reprogramming

Cell potency

10.1038/nrg3473