Recommended Readings: Leonard Zon, M.D.

Monday, November 4, 2013
4:00 p.m., Carson Family Auditorium

Leonard Zon, M.D.
Director of the Stem Cell Program at Children’s Hospital Boston
Grousbeck Professor of Pediatric Medicine, Harvard Medical School
Investigator, Howard Hughes Medical Institute

Pathways that Stimulate Stem Cell Development and Self-Renewal

Recommended Readings:

Review Papers

De Jong, J. L. O., & Zon, L. I. (2005). Use of the zebrafish system to study primitive and definitive hematopoiesis. Annual Review of Genetics, 39, 481–501. doi:10.1146/annurev.genet.39.073003.095931

Orkin, S. H., & Zon, L. I. (2008). Hematopoiesis: an evolving paradigm for stem cell biologyCell132(4), 631–644. doi:10.1016/j.cell.2008.01.025

White, R., Rose, K., & Zon, L. (2013). Zebrafish cancer: the state of the art and the path forward. Nature Reviews Cancer, 13(9), 624–636. doi:10.1038/nrc3589

Zon, L. I. (2008). Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature, 453(7193), 306–313. doi:10.1038/nature07038

Empirical Articles

Goessling, W., North, T. E., Loewer, S., Lord, A. M., Lee, S., Stoick-Cooper, C. L., … Zon, L. I. (2009). Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell, 136(6), 1136–1147. doi:10.1016/j.cell.2009.01.015

Lengerke, C., Schmitt, S., Bowman, T. V, Jang, I. H., Maouche-Chretien, L., McKinney-Freeman, S., … Daley, G. Q. (2008). BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway. Cell Stem Cell, 2(1), 72–82. doi:10.1016/j.stem.2007.10.022

North, T. E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A. M., … Zon, L. I. (2009). Hematopoietic stem cell development is dependent on blood flow. Cell, 137(4), 736–748. doi:10.1016/j.cell.2009.04.023

North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., … Zon, L. I. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 447(7147), 1007–1011. doi:10.1038/nature05883

Recommended Readings: Richard A. Young, Ph.D.

Friday Lecture Series

Cancer Biology Lecture

Transcriptional Control of Cell Identity

Richard A. Young, Ph.D., professor of biology and member,

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

May 17, 2013

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

Recommended Readings

Guenther, M. G., & Young, R. A. (2010). Repressive transcription. Science, 329(5988), 150-151

Jaenisch, R., & Young, R. (2008). Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell, 132(4), 567-582

Mazzoni, E. O., Mahony, S., Iacovino, M., Morrison, C. A., Mountoufaris, G., Closser, M., . . . Wichterle, H. (2011). Embryonic stem cell-based mapping of developmental transcriptional programs. Nature Methods, 8(12), 1056-1060

Newman, J. J., & Young, R. A. (2010). Connecting transcriptional control to chromosome structure and human disease. Cold Spring Harbor Symposia on Quantitative Biology 75 , pp. 227-235

Novershtern, N., Subramanian, A., Lawton, L. N., Mak, R. H., Haining, W. N., McConkey, M. E., . . . Ebert, B. L. (2011). Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell, 144(2), 296-309

Young, R. A. (2011). Control of the embryonic stem cell state. Cell, 144(6), 940-954


Recommended Readings: Elaine Fuchs, Ph.D.

Friday Lecture Series

Skin Stem Cells: In Morphogenesis, Wound Repair and Cancer

Elaine Fuchs, Ph.D., Rebecca C. Lancefield Professor,

The Rockefeller University

March 2, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium


Recommended Readings:

Blanpain, C., and E. Fuchs. 2009. Epidermal homeostasis: A balancing act of stem cells in the skin. Nature Reviews Molecular Cell Biology 10, (3): 207-217

Ezhkova, E., W. -H Lien, N. Stokes, H. A. Pasolli, J. M. Silva, and E. Fuchs. 2011. EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair. Genes and Development 25, (5): 485-498

Fuchs, E. 2007. Scratching the surface of skin development. Nature 445, (7130): 834-842

Guasch, G., M. Schober, H. A. Pasolli, E. B. Conn, L. Polak, and E. Fuchs. 2007. Loss of TGFβ signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12, (4): 313-327

Kobielak, A., and E. Fuchs. 2006. Links between α-catenin, NF-κB, and squamous cell carcinoma in skin. Proceedings of the National Academy of Sciences of the United States of America 103, (7): 2322-2327

Williams, S. E., S. Beronja, H. A. Pasolli, and E. Fuchs. 2011. Asymmetric cell divisions promote notch-dependent epidermal differentiation. Nature 470, (7334): 353-358

Yi, R., and E. Fuchs. 2010. MicroRNA-mediated control in the skin. Cell death and differentiation 17, (2): 229-235

Recommended Readings: Jeannie T. Lee, M.D., Ph.D.

Friday Lecture Series

Richard M. Furlaud Distinguished Lecture

X-Chromosome Inactivation as a Model for Epigenomic Regulation by Long

Noncoding RNAs

Jeannie T. Lee, M.D., Ph.D., professor of genetics and pathology,

Harvard Medical School, investigator,

Howard Hughes Medical Institute

January 27, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

Recommended Readings:

Lengner, C. J., A. A. Gimelbrant, J. A. Erwin, A. W. Cheng, M. G. Guenther, G. G. Welstead, R. Alagappan, et al. 2010. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141, (5): 872-883

Namekawa, S. H., B. Payer, K. D. Huynh, R. Jaenisch, and J. T. Lee. 2010. Two-step imprinted X inactivation: Repeat versus genic silencing in the mouse. Molecular and cellular biology 30, (13): 3187-3205

Sarma, K., P. Levasseur, A. Aristarkhov, and J. T. Lee. 2010. Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of xist RNA localization to the X chromosome. Proceedings of the National Academy of Sciences of the United States of America 107, (51): 22196-22201

Tian, D., S. Sun, and J. T. Lee. 2010. The long noncoding RNA, jpx, is a molecular switch for X chromosome inactivation. Cell 143, (3): 390-403

Zhou, D., C. Conrad, F. Xia, J. -S Park, B. Payer, Y. Yin, G. Y. Lauwers, et al. 2009. Mst1 and Mst2 maintain hepatocyte quiescence and Suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16, (5): 425-438

U.K. Establishes New Stem Cell Center

The British government has given its approval for the creation of a £30 million stem cell therapy center, part of a £220 million program to turn British stem cell researchers’ discoveries into “a new multimillion-pound industry to help drive Britain’s recovery,” reports the Guardian‘s Rupert Neate. The stem cell center, which is slated to open in April 2012, will take advantage of the UK’s leadership in stem cell research, Neate says. The researchers will work to manufacture therapies for everything from Parkinson’s disease to prostate cancer. A third of the money will come from the British government, another third from the European Union, and the rest from companies like Pfizer and AstraZeneca, which are contracting to use part of the site where the center will be located. “It will have a test manufacturing facility to help labs convert a couple of grams of potentially life-saving cells into kilos of the stuff that can be sold commercially,” David Bott, director of innovation at the Technology Strategy Board, tells Neate.

New Open Access Stem Cell-Omics Database

Scientists at the University of Wisconsin-Madison have launched an open-access database for collecting and analyzing quantitative information about pluripotent stem cells, including data on mRNA, protein, and post-translational modifications.

Named the Stem Cell -Omics Repository, the resource was launched this week to coincide with a study published in Nature Methods comparing the proteomes and phosphoproteomes of human embryonic and induced pluripotent stem cells.

In addition to providing this protein-level comparison, the paper lays out a proteomic workflow using a relatively large number of samples and biological replicates to draw out subtle but potentially important differences between similar cell types, said study leader Joshua Coon, UW-Madison assistant professor

For the stem-cell work the researchers “combined high accuracy mass spectrometry and isobaric tagging on a large scale” in a way that let them compare proteins and phosphorylation sites across four ESC lines and four iPSC lines in biological triplicate. This enabled them to identify differences between the lines that would otherwise have gone undetected.

Deep Comparison Reveals Similarities Between Pluripotent and Embryonic Stem Cells

Researchers at the University of Wisconsin, using a combination of techiques, conducted a rigorous analysis of  ESC’s and iPSC’s revealing significant and functionally related differences.   Their research also resulted in the establishment of a new online resource named SCOR for storing and searching data on pluripotency.   Read more in NATURE METHODS. 

Two Types of Bone Marrow Stem Cells Could Work Together to Advance Regenerative Medicine

ScienceDaily (Aug. 16, 2010) — A study led by a researcher at Albert Einstein College of Medicine of Yeshiva University has revealed a unique “partnership” between two types of bone marrow stem cells, which could lead to advances in regenerative medicine.  The study was led by Paul Frenette, M.D., the new director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein. Dr. Frenette conducted the research while at Mt. Sinai School of Medicine in New York City.  The research was published in the Aug 12 issue of Nature.

Discovering the Origin of Adult Blood Stem Cells

ScienceDaily (Feb. 16, 2010) — Biologists at UC San Diego have identified the specific region in vertebrates where adult blood stem cells arise during embryonic development.     Their discovery, which appears in a paper in this week’s early online edition of the journal Nature, is a critical first step for the development of safer and more effective stem cell therapies for patients with leukemia, multiple myeloma, anemia and a host of other diseases of the blood or bone marrow.

Read the details in early online publication in NATURE.

2009 “Hottest biology papers”

Of the five “hottest” papers of 2009 in biology, three were published in NATURE, two in CELL.  The topics are no surprise: genomics and stem cells.   Click and read:

1. K. Takahashi, et al.,Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, 131: 861-72, 2007.
Citations this year: 520
Total citations to date: 886
Findings: This work from Shinya Yamanaka’s lab in Japan was the first to demonstrate that induced pluripotent stem (iPS) cells can be generated from adult human dermal fibroblasts. Previous efforts by the team showed that iPS cells could be derived from mouse somatic cells
2. K.A. Frazer, et al.,A second generation human haplotype map of over 3.1 million SNPs,” Nature, 449: 854-61, 2007.
Citations this year: 389
Total citations to date: 588
Findings: Since the sequencing of the human genome in 2003, the International HapMap Project has explored single nucleotide polymorphisms (SNPs) — differences in a single letter of the DNA — to study how these small variations affect the development of diseases and the body’s response to pathogens and drugs. HapMap I, the original report, placed one SNP at roughly every 5,000 DNA letters. The newest map, featured in this paper, sequenced an additional 2 million SNPs, increasing the map’s resolution to one SNP per kilobase. The additional detail allows scientists to more closely investigate patterns in SNP differences, especially in hotspot regions, or concentrated stretches of DNA.

3. A. Barski, et al.,High-resolution profiling of histone methylations in the human genome,” Cell, 129: 823-37, 2007.
Citations this year: 299
Total citations to date:: 560
Findings: This study looked at how histone modifications influence gene expression in more detail than previous attempts. Using a powerful sequencing tool called Solexa 1G, the researchers mapped more than 20 million DNA sequences associated with specific forms of histones, finding there were differences in methylation patterns between stem cells and differentiated T cells.

4. E. Birney, et al.,Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, “Nature, 447: 799-816, 2007.
Citations this year: 267
Total citations to date: 618
Findings: The ENCODE project — ENCODE stands for the ENCyclopedia Of DNA Elements — set out to identify all functional elements in the human genome. After examining one percent of the genome, the paper revealed several new insights about how information encoded in the DNA comes to life in a cell.

5. A M. Wernig, et al.,In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state,” Nature 448: 318-24, 2007.
Citations this year: 237
Total citations to date: 512
Findings: Scientists successfully performed somatic-cell nuclear transfer (SCNT), producing stem cell lines and cloned animals for the first time using fertilized mouse eggs.