STEM CELL BIOLOGY
COURSE INFO:
Medical school: G16.4413/GSAS: G23.2128
Course Organizer: E. Jane Hubbard, Associate Professor jhubbard@saturn.med.nyu.edu
COURSE GOALS:
Stem cell biology lies at the intersection of developmental/cell biology and medicine. It has direct relevance to cancer and holds promise for regenerative medicine. One challenge in the field is the background required to stay abreast of progress is being made in divergent organisms and organ systems using a host of techniques. This course - in its breadth and emphasis on molecular underpinnings and rigorous data interpretation - aims to meet this challenge.
COURSE DESCRIPTION:
This course will cover a broad range of topics relevant to stem cell biology. This fast-moving field brings together many aspects of basic and applied biology and medicine including development, regeneration/repair, and cancer. The course will cover these topics in four parts: concepts and themes (including adult, embryonic, germline stem cells, general molecular themes), stem cell biology relevant to specific organ systems, stem cells and cancer, and therapeutics and ethics. The lecture/discussion format will give students both a broad background and the opportunity to apply critical thinking skills to recent data in the field.
COURSE LOGISTICS:
6 credits. Prerequisites: Completion of first three semesters of graduate curriculum of the Sackler graduate program, Biology graduate program, or equivalent (postdocs may attend Tuesday lectures only). Permission of instructor required for non-Sackler students.
GRADING:
Will be based on active participation in discussion sessions and on a final paper. Final paper will be in the format of an original short proposal describing 1-2 follow-up experiments that derive from the class discussion sessions. Papers must be written independently and in your own words, but you may discuss the proposed experiment(s) with faculty and/or classmates. Papers are due the at the last class meeting. Limit is 5 pages; include a clear statement of the question, relevant background, experimental design and methods, expected results and interpretation, alternative possible results and interpretation, and references.
Relevant programs: Cellular and Molecular Biology, Developmental Genetics, Molecular Oncology and Immunology, Molecular Pharmacology, Pathobiology, Neuroscience and Physiology; other GSAS programs: Department of Biology
Format: spring semester – 5-7pm Tuesdays and Thursdays (Tuesdays: MSB room 393 – Biochemistry lecture hall, Thursdays: 4th floor conference room, Skirball Institute building)
2-hr Lecture (usually team of 2 lecturers)
2-hr Discussion (current primary literature-based; may include presentations; students will be graded on preparation and participation)
Resources: No textbook is available, as can be expected in this very new, fast-moving field. As the course progresses, lecturers will compile and update a set of useful comprehensive high-quality review articles (e.g, from Cell, Nature and Science, and other journals including “special issues” or special sections on stem cell biology). Future: a web-based stem cell information resource as a bi-product of the course.
Week 1:
Introduction and concepts in Stem cell biology
Jan 29, 2008
Jane Hubbard and Lynn Wilson
Assigned papers for week 1:
1.) McCulloch EA, Till JE
The Radiation Sensitivity of Normal Mouse Bone Marrow Cells, Determined by Quantitative Marrow Transplantation into Irradiated Mice
Radiation Research, Vol. 13, No. 1. (Jul., 1960), pp. 115-125.
http://www.ncbi.nlm.nih.gov/pubmed/13858509
2.) Becker AJ, McCulloch EA, Till JE
Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells.
Nature. 1963 Feb 2;197:452-4.
http://www.ncbi.nlm.nih.gov/pubmed/13970094
3.) Mintz B, Illmensee K
Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585-9.
http://www.ncbi.nlm.nih.gov/pubmed/1059147
4.) Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH.
Viable offspring derived from fetal and adult mammalian cells.
Nature. 1997 Feb 27;385(6619):810-3. Erratum in: Nature 1997 Mar 13;386(6621):200.
http://www.ncbi.nlm.nih.gov/pubmed/9039911
Week 2
Embryonic Stem cells
Feb 5, 2008
Lisa Dailey and Chris Hansis
Assigned papers for week 2:
1.) Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872.
http://www.ncbi.nlm.nih.gov/pubmed/18035408
2.) Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R (2006) Human embryonic stem cell lines derived from single blastomeres. Nature 444, 481-485.
http://www.ncbi.nlm.nih.gov/pubmed/16929302
Week 3:
Germline stem cells
Feb 12, 2008
Ruth Lehmann and Jane Hubbard
Assigned papers for week 3:
1.) Yamashita YM, Mahowald AP, Perlin JR, Fuller MT.
Asymmetric inheritance of mother versus daughter centrosome in stem cell division.
Science. 2007 Jan 26;315(5811):518-21.
http://www.ncbi.nlm.nih.gov/pubmed/17255513
2.) Seandel M, James D, Shmelkov SV, Falciatori I, Kim J, Chavala S, Scherr DS, Zhang F, Torres R, Gale NW, Yancopoulos GD, Murphy A, Valenzuela DM, Hobbs RM, Pandolfi PP, Rafii S. Generation of functional multipotent adult stem cells from GPR125+ germline progenitors.Nature. 2007 Sep 20;449(7160):346-50.
http://www.ncbi.nlm.nih.gov/pubmed/17882221
Week 4
Neuronal stem cells
Feb 19, 2008
Gord Fishell and Jeremy Dasen
Assigned papers for week 4:
1.) Andersson E, Tryggvason U, Deng Q, Friling S, Alekseenko Z, Robert B, Perlmann T, Ericson J.
Identification of intrinsic determinants of midbrain dopamine neurons.
Cell. 2006 Jan 27;124(2):393-405.
http://www.ncbi.nlm.nih.gov/pubmed/16439212
2.) Merkle FT, Mirzadeh Z, Alvarez-Buylla A. Mosaic organization of neural stem cells in the adult brain.
Science. 2007 Jul 20;317(5836):381-4.
http://www.ncbi.nlm.nih.gov/pubmed/17615304
Week 5:
Telomeres
Feb 26, 2008
Susan Smith
Assigned papers for week 5:
1.) Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, Artandi MK, Oro AE, Artandi SE.
Conditional telomerase induction causes proliferation of hair follicle stem cells.
Nature. 2005 Aug 18;436(7053):1048-52.
http://www.ncbi.nlm.nih.gov/pubmed/16107853
Week 6:
Mesenchymal and Cardiac Stem cells
March 4, 2008
Eva Hernando and Debbie Yelon
Assigned papers for week 6:
1.) Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P.
Bone marrow cells regenerate infarcted myocardium.
Nature. 2001 Apr 5;410(6829):701-5.
http://www.ncbi.nlm.nih.gov/pubmed/11287958
2.) Barberi T, Bradbury M, Dincer Z, Panagiotakos G, Socci ND, Studer L.Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nat Med. 2007 May;13(5):642-8. Epub 2007 Apr 8.
http://www.ncbi.nlm.nih.gov/pubmed/17417652
3.) Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA.
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007 Oct 4;449(7162):557-63.
http://www.ncbi.nlm.nih.gov/pubmed/17914389
Week 7:
Hematopoietic Stem Cells
March 11, 2008
Iannis Aifantis
Assigned papers for week 7:
1.) Wilson A, Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, Oser GM, Pasche AC, Knabenhans C, Macdonald HR, Trumpp A.
c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.
Genes Dev. 2004 Nov 15;18(22):2747-63.
http://www.ncbi.nlm.nih.gov/pubmed/15545632
2.) Wu M, Kwon HY, Rattis F, Blum J, Zhao C, Ashkenazi R, Jackson TL, Gaiano N, Oliver T, Reya T.
Imaging hematopoietic precursor division in real time.
Cell Stem Cell. 2007 Nov 15;1(5):541-54.
http://www.ncbi.nlm.nih.gov/pubmed/18345353
3.) Ara T, Tokoyoda K, Sugiyama T, Egawa T, Kawabata K, Nagasawa T. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny.
Immunity. 2003 Aug;19(2):257-67.
http://www.ncbi.nlm.nih.gov/pubmed/12932359
Week 8:
Skin and Intestine Stem Cells
March 25, 2008
Ram DasGupta and Pam Cowin
Assigned papers for week 8:
1.) Fuchs E, Skin stem cells: rising to the surface. The Journal of Cell Biology, Vol. 180, No. 2, January 28, 2008 273–284
http://www.jcb.org/cgi/doi/ JCB 273 10.1083/jcb.200708185
2.) Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H.
Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007 Oct 25;449(7165):1003-7. Epub 2007 Oct 14.
http://www.ncbi.nlm.nih.gov/pubmed/17934449
Week 9:
Breast and Prostate Stem Cells
April 1, 2008
Pam Cowin and Lyn Wilson
Assigned papers for week 9:
1.) Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE.
Generation of a functional mammary gland from a single stem cell.
Nature. 2006 Jan 5;439(7072):84-8.
http://www.ncbi.nlm.nih.gov/pubmed/16397499
2.) Salm SN, Burger PE, Coetzee S, Goto K, Moscatelli D, Wilson EL.
TGF-{beta} maintains dormancy of prostatic stem cells in the proximal region of ducts. J Cell Biol. 2005 Jul 4;170(1):81-90. http://www.ncbi.nlm.nih.gov/pubmed/15983059
Week 10:
Cancer Stem Cells
April 8, 2008
Eva Hernando, Iannis Aifantis, Dafna Bar-Sagi
Assigned papers for week 10:
1.) Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, Huelsken J.
Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling.
Nature. 2008 Apr 3;452(7187):650-3.
http://www.ncbi.nlm.nih.gov/pubmed/18385740
2.) Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T.
Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005 Jun 17;121(6):823-35.
http://www.ncbi.nlm.nih.gov/pubmed/15960971
Supporting material:
Dalerba P, Cho RW, Clarke MF.
Cancer stem cells: models and concepts.
Annu Rev Med. 2007;58:267-84. Review.
http://www.ncbi.nlm.nih.gov/pubmed/17002552
Week 11:
Cancer Stem Cells II
April 15, 2008
Iannis Aifantis
Assigned papers for week 11:
1.) Kern SE, Shibata D. The fuzzy math of solid tumor stem cells: a perspective. Cancer Res. 2007 Oct 1;67(19):8985-8. http://www.ncbi.nlm.nih.gov/pubmed/17908998
Week 12:
Stem Cells and Therapeutics
April 22, 2008
Shahin Rafii (Cornell Medical Center)
Assigned papers for week 12:
1.) Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G.
Pluripotency of spermatogonial stem cells from adult mouse testis.
Nature. 2006 Apr 27;440(7088):1199-203. http://www.ncbi.nlm.nih.gov/pubmed/16565704
2.) Seandel M, James D, Shmelkov SV, Falciatori I, Kim J, Chavala S, Scherr DS, Zhang F, Torres R, Gale NW, Yancopoulos GD, Murphy A, Valenzuela DM, Hobbs RM, Pandolfi PP, Rafii S.
Generation of functional multipotent adult stem cells from GPR125+ germline progenitors.
Nature. 2007 Sep 20;449(7160):346-50.
http://www.ncbi.nlm.nih.gov/pubmed/17882221
Week 13A:
Stem Cells and Ethics
April 29, 2008
William Ruddick (NYU Department of Philosophy)
Assigned papers for week 13A:
1.) Gruen L, Grabel L.
Concise review: scientific and ethical roadblocks to human embryonic stem cell therapy.
Stem Cells. 2006 Oct;24(10):2162-9. Review.
http://www.ncbi.nlm.nih.gov/pubmed/16794263
2.) George, R
Embryo ethics.
Daedalus. Winter 2008, American Academy of Arts and Sciences
http://www.mitpressjournals.org/toc/daed/137/1
3.) Devolder K , Harris J
The Ambiguity of the Embryo: Ethical inconsistency in the human embryonic stem cell debate.
Metaphilosopy. Vol. 38, Nos. 2–3, April 2007 pp. 153-169.
http://www.blackwell-synergy.com/toc/meta/38/2-3
Week 13B:
Chromatin (moved from week 5)
May 1, 2008
Danny Reinberg
Assigned papers for week 13B:
1.) Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES.
A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006 Apr 21;125(2):315-26.
http://www.ncbi.nlm.nih.gov/pubmed/16630819
2.) Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE.
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007 Aug 2;448(7153):553-60. Epub 2007 Jul 1.
http://www.ncbi.nlm.nih.gov/pubmed/17603471
3.) Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R.
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007 Jul 19;448(7151):318-24. Epub 2007 Jun 6.
http://www.ncbi.nlm.nih.gov/pubmed/17554336
4.) Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S.
Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells. Science. 2008 Feb 14; [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/18276851
5.) Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M, Gifford DK, Young RA, Jaenisch R.
Polycomb complexes repress developmental regulators in murine embryonic stem cells.
Nature. 2006 May 18;441(7091):349-53. Epub 2006 Apr 19.
http://www.ncbi.nlm.nih.gov/pubmed/16625203
6.) Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, Koseki H, Fuchikami T, Abe K, Murray HL, Zucker JP, Yuan B, Bell GW, Herbolsheimer E, Hannett NM, Sun K, Odom DT, Otte AP, Volkert TL, Bartel DP, Melton DA, Gifford DK, Jaenisch R, Young RA.
Control of developmental regulators by Polycomb in human embryonic stem cells.
Cell. 2006 Apr 21;125(2):301-13.
http://www.ncbi.nlm.nih.gov/pubmed/16630818
7.) Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA.
A chromatin landmark and transcription initiation at most promoters in human cells.Cell. 2007 Jul 13;130(1):77-88.
http://www.ncbi.nlm.nih.gov/pubmed/17632057