4th NIGMS Workshop on Human Embryonic Stem Cell Research: Recent Progress and Future Directions of NIGMS Grantees

October 18-19, 2011

Workshop Summary

This workshop was held to enable NIGMS grantees working on human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) to meet and discuss recent research findings and to identify and explore the problems, challenges and opportunities of these exciting research areas. Among the 69 attendees were 63 NIGMS grantees and 6 NIH staff members. Most of the grantees were members of five Program Projects for Basic Research on Human Embryonic Stem Cells or three newly-awarded Program Projects on the Basic Biology of Pluripotency and Reprogramming.

The talks and posters focused on four broad areas of hESC and iPSC research: pluripotency and self-renewal, technological approaches, differentiation mechanisms and epigenetics and reprogramming. Following one and a half days of scientific presentations, the workshop concluded with a lively discussion that focused on three areas which are critical for the future of this field.

  • Biological questions: What does it mean to be a stem cell? Has the core circuitry of pluripotency been defined, and how do we know when it is complete? Are there different pluripotent states, and how dynamic and heterogeneous are they? What is the significance of bivalency (promoters marked with both activating and repressive chromatin modifications) in pluripotent cells? What are the similarities and differences between in vitro generated cells and their in vivo counterparts? How mature are in vitro derived cells? What is the relationship of ESC to somatic stem cells or germ cells-are there common mechanisms or common genes? What is the relationship between pluripotency and cancer? What can we learn about chromosome biology and mitochondria by studying ESC and iPSC?
  • Technical issues and needs: quality control for cell lines and data; rigorous assays for pluripotency (teratoma assay/-score-card-); efficient and safe reprogramming tools (new vectors and/or small molecules); effective differentiation protocols for many different lineages; methods to ensure immune tolerance; reporters and lineage tracing techniques for human cells. How can we identify fully reprogrammed iPSC? What is the relationship between hESC, iPSC and cells of the embryo? How stable are the genome and epigenome of hESC and iPSC, what level of alteration is acceptable for clinical use, and how do we assess risk? How does natural human variation affect clinical use of these cells?
  • Needed supporting technologies and resources: suitable animal models for testing therapies; human trophoblastic stem cell lines; gene expression atlas for early post-implantation stage primate embryos; antibodies against all human proteins; access to engineering, clinical translational support, instrumentation and trained personnel for -omics approaches and bioinformatics; non-destructive analytic tools; technological improvements to enable metabolomic and mass spectrometry analysis of small numbers of cells.

The full agenda and list of participants are below.

Agenda

Tuesday, October 18, 2011
Natcher Conference Center Room F1/F2

7:45 - 8:15 AMMorning refreshments
8:15 - 8:30 AM Welcome and Introduction
Judith Greenberg
8:30 - 10:00 AM Session I: Pluripotency and self-renewal I
Chair: Jamie Thomson
8:30 - 8:50 AM Ronin and regulation of ES cell self-renewal
Thomas Zwaka
8:50 - 9:10 AM A novel Nanog complex involved in ES cell pluripotency
Zhou Songyang
9:10 - 9:30 AM Cell signaling pathways in human pluripotent cells
Amar Singh
9:30 - 9:50 AM p53 interactions in maintenance and differentiation of ES cells
Michelle Barton
9:50 - 10:00AM Discussion
10:00 - 10:30 AMBreak
10:30 - 11:50 AM Session II Pluripotency and self-renewal II
Chair: Tony Blau
10:30 - 10:50 AM GCNF circuitry in iPS cell formation and ES cell differentiation
Austin Cooney
10:50 - 11:10 AM Epigenetic variation in human embryonic stem cell lines with age
Amander Clark
11:10 - 11:30 AM An evolutionarily conserved program for stem cell dormancy
Tony Blau
11:30 - 11:50 AM Molecular and architectural mechanisms of reprogramming to pluripotency
Kathrin Plath
11:50 - 12:00 PM Discussion
12:00 - 1:00 PM Lunch and informal discussions
1:00 - 3:00 PM Session III: Technological Approaches
Chair: Jerome Zack
1:00 - 1:20 PM Technologies for the genome age
Lloyd Smith
1:20 - 1:40 PM Proteomic analysis of human ES, iPS, and somatic cells
Justin Brumbaugh
1:40 - 2:00 PM Glycan analysis of human pluripotent stem cells
Lance Wells
2:00 - 2:20 PM Spatially and chemically defined platform for the growth of pluripotent cells
April Pyle
2:20 - 2:40 PM Suspension culture and drug screening
Tom Schulz
2:40 - 3:00 PM Dissecting the establishment and regulation of pluripotency
Alex Meissner
3:00 - 3:15 PM Discussion
3:15 - 5:30 PM Poster Session and refreshments
Natcher Conference Center Atrium

Wednesday, October 19, 2011
Natcher Conference Center Room F1/F2

7:30 - 8:10 AM Morning refreshments
8:10 - 10:00 AM Session IV: Differentiation mechanisms
Chair: Stephen Dalton
8:10 - 8:30 AM Wnt signaling and stem cell biology
Kathy Davidson
8:30 - 8:50 AM FGF signaling in mesendoderm differentiation of human ES cells
Pengzhi Yu
8:50 - 9:10 AM A developmental yardstick for pluripotent stem cells.
Hannele Ruohola-Baker
9:10 - 9:30 AM Microarray characterization of human ESC derived retinal cells
Anna La Torre
9:30 - 9:50 AM Molecular bottlenecks limiting the generation of functional HSCs from hESCs
Maria Sierra
9:50 - 10:00AM Discussion
10:00 - 10:30 AMBreak
10:30 - 12:00 PM Session V: Epigenetics and Reprogramming I
Chair: Margaret Goodell
10:30 - 10:50 AM Epigenetics of pluripotent stem cell derived cardiomyocytes
Lil Pabon
10:50 - 11:10 AM DNA replication and epigenetics
David Gilbert
11:10 - 11:30 AM Reprogramming of blood cells to pluripotency
Igor Slukvin
11:30 - 11:50 AM Epigenetic regulation of human pluripotent cells
Hengbin Wang
11:50 - 12:00 PM Discussion
12:00 - 1:00 PM Lunch and informal discussions
1:00 - 3:30 PM Session VI: Epigenetics and Reprogramming II
Chair: Margaret Goodell
1:00 - 1:20 PM The role of DNA methylation in stem cell gene regulation and reprogramming
Guoping Fan
1:20 - 1:40 PM Longitudinal epigenomic tracking of the reprogramming process
Joseph Wu
1:.40 - 1:50 PM Discussion
1:50 - 3:30 PM Session V: Future Directions and Challenges
Chair: Marion Zatz and Susan Haynes
2:00 - 2:30 PM Commentary
Jamie Thomson
2:30 - 2:45 PM The NIH Center for Regenerative Medicine (NIH-CRM)
Mahendra Rao
2:45 - 3:30 PM Discussion: The future of pluripotential stem cell research
3:30 PM Adjourn

Workshop Participants

(Contact information as provided by the participants)

Kadir Akdemir
Graduate Student
Biochemistry
MD Anderson Cancer Center
1515 Holcombe Blvd
Houston, TX 77030
Email: kcakedemir@mdanderson.org

Mirit Aladjem, PHD
NCI
37 Convent Drive
Bethesda, MD 20892
Email: aladjemm@mail.nih.gov

Kendra Allton
UT MD Anderson Cancer Center
11800 City Park Central Lane
#427
Houston, TX 77047
Email: kallton@mdanderson.org

Michelle Barton, PHD
Professor
Biochemistry & Molecular Biology
UT MD Anderson Cancer Center
1515 Holcombe Boulevard
Unit 1000
Houston, TX 77030
Tel: 713-834-6268
Fax: 713-834-6273
Email: mbarton@mdanderson.org

Tony Blau, MD
Hematology
University of Washington
815 Mercer Street
Box 358056
Seattle, WA 98109
Tel: 206-685-6873
Email: tblau@uw.edu

Justin Brumbaugh
University of Wisconsin
425 Henry Mall
Madison, WI 53706
Email: brumbaugh@wisc.edu

Christa Buecker, PHD
Chemical and Systems Biology
Stanford School of Medicine
269 Campus Drive
CCSR, Rm. 3130
Stanford, CA 94305
Email: cbuecker@stanford.edu

David Chan
Graduate Student
MCDB
UCLA
621 Charles E. Young Drive South
Room 2204 (Lowry Lab)
Los Angeles, CA 90095
Tel: 714-721-8652
Email: davidchan@ucla.edu

James Chappell
Graduate Student
Biochemistry and Molecular Biology
University of Georgia
180 Normal Avenue
Athens, GA 30606
Tel: 770-789-3786
Email: jchap14@gmail.com

Amander Clark
Assistant Professor
UCLA
University of California, Los Angeles
621 Charles E Young Drive South
Los Angeles, CA 90095
Email: clarka@ucla.edu

Tim Cliff
Graduate Student
Biochemistry and Molecular Biology
University of Georgia
Paul D Coverdell Center
Room 276
500 D.W. Brooks Drive
Athens, GA 30602
Tel: 706-583-8145
Email: clifftim@uga.edu

Joshua Coon
University of Wisconsin
425 Henry Mall
Madison, WI 53706
Email: jcoon@chem.wisc.edu

Austin Cooney, PHD
Associate Professor
Molecular and Cellular Biology
Baylor College of Medicine
4530 Elm Street
Bellaire, TX 77401
Tel: 713-798-6250 ext.713-798
Fax: 713-798-6250
Email: acooney@bcm.edu

Stephen Dalton
Biochemistry and Molecular Biology
University of Georgia
Paul D. Coverdell Center
500 DW Brooks Drive, Rm245
Athens, GA 30602
Tel: 706-583-0480
Email: sdalton@uga.edu

Kathryn Davidson, PHD
Post-doctoral Fellow
HHMI & Department of Pharmacology
University of Washington
University of Washington School of Medicine, ISCRM
Campus Box 358056, Room S576
815 Mercer St
Seattle, WA 98109
Tel: 206-543-5519
Email: davidsok@u.washington.edu

Kevin Eggan
Associate Professor
Stem Cell & Regenerative Biology
Harvard University
7 Divinity Avenue
Suite #258
Cambridge, MA 02138
Tel: 617-496-5611
Email: keggan@scrb.harvard.edu

Guoping Fan, PHD
Professor
Human Genetics
UCLA
695 Charles Young Drive South
Los Angeles, CA 90095
Email: gfan@mednet.ucla.edu

Elsa Flores, PHD
Associate Professor
Biochemistry & Molecular Biology
U.T. M.D. Anderson Cancer Center
1515 Holcombe Boulevard
Unit 1000
Houston, TX 77030
Tel: 713-792-0413
Email: elsaflores@mdanderson.org

Zoran Galic, PHD
Medicine
UCLA
3135 Terasaki Life Sciences Building
610 Charles E. Young Drive East
Los Angeles, CA 90095
Tel: 310-825-4671
Email: zgalic@ucla.edu

David Gilbert, PHD
Professor
Biological Science
Florida State University
319 Stadium Drive
Tallahassee, FL 32306
Email: gilbert@bio.fsu.edu

Margaret Goodell, PHD
Professor
Pediatrics, Hematology/Oncology
Baylor College of Medicine
One Baylor Plaza, BCM505
Houston, TX 77030
Tel: 713-798-1265
Fax: 713-798-1230
Email: goodell@bcm.edu

Judith Greenberg, PHD
Acting Director, NIGMS
NIGMS, NIH
Building 45, Room 2An12
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Email: greenbej@nigms.nih.gov

Ji Han, PHD
Post-doctoral Research Fellow
Medicine
Emory University
101 Woodruff Circle
WMB 2103
Atlanta, GA 30322
Tel: 404-441-7304
Fax: 404-712-1729
Email: ji.han@emory.edu

Susan Haynes, PHD
Program Director
Division of Genetics & Developmental Biology
NIGMS, NIH
45 Center Dr. MSC 6200
Bethesda, MD 20892-6200
Tel: 301-594-0943
Fax: 301-480-2228
Email: hayness@nigms.nih.gov

Abhinav Jain, PHD
Post-doctoral Fellow
Biochemistry & Molecular Biology
U T M D Anderson Cancer Center
1515 Holcombe Blvd
Unit 1000
Houston, TX 77054
Email: ajain@mdanderson.org

Anna La Torre, PHD
Biological Structure
University of Washington - ISCRM
815 Mercer Street, Room S541
Seattle, WA 98195
Tel: 206-221-0605
Email: annalt@u.washington.edu

Patricia Labosky, PHD
Associate Professor
Vanderbilt University Medical Center
Center for Stem Cell Biology
9415D MRB IV
2213 Garland Avenue
Nashville, TN 37232-0494
Tel: 615-322-2540
Email: trish.labosky@vanderbilt.edu

Scott Lipnick, PHD
NIH CRM
2923 Tilden Street, NW
Washington, DC 20008
Email: lipnicksl@mail.nih.gov

Elena Mancini, PHD
Genetics
Stanford University
Alway Building, M336
Stanford University School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Email: mancini@stanford.edu

Lilyana Margaretha
Graduate Student
Hematology & MCB
University of Washington
UW ISCRM, 815 Mercer St, Room N530
Seattle, WA 98109
Tel: 206-543-3363
Email: lilyanam@uw.edu

Julie Mathieu, PHD
Biochemistry
University of Washington
UW Medicine at South Lake Union
815 Mercer Street
Seattle, WA 98109
Tel: 206-543-1710
Email: jmathieu@u.washington.edu

Alexander Meissner
Harvard University
7 Divinity Avenue
Cambridge, MA 02138
Email: alexander_meissner@harvard.edu

Laura Menendez, PHD
Post-doctoral Associate
Biochemistry and Molecular Biology
University of Georgia
Paul D. Coverdell Center, Room 276
500 DW Brooks Drive
University of Georgia
Athens, GA 30602
Email: lmenen@uga.edu

Tarjei Mikkelsen, PHD
HSCI/Broad Institute
7 Cambridge Center
Room 6047B
Cambridge, MA 02142
Email: tarjei@broadinstitute.org

Kazu Murata, PHD
Stanford University
Lil Pabon, PHD
University of Washington
Center for Cardiovascular Biology-UW
815 Mercer Street
Seattle, WA 98109
Email: lmp@u.washington.edu

Xinghua Pan, PHD
Research Scientist
Genetics
Yale University School of Medicine
PO Box 208005
New Haven, CT 06520
Tel: 203 589 1087
Email: xinghua.pan@yale.edu

Kathrin Plath, PHD
Associate Professor
Biological Chemistry
UCLA School of Medicine
615 Charles E. Young Drive South
BSRB 390D
Los Angeles, CA 90095
Tel: 310-2068688
Email: kplath@mednet.ucla.edu

April Pyle, PHD
MIMG/BROAD STEM CELL
UCLA
UCLA/Department of MIMG/BROAD STEM CELL
277A BSRB
615 Charles E. Young Dr. S
Los Angeles, CA 90095
Email: apyle@mednet.ucla.edu

Mahendra Rao, MD, PHD, PHD
Director NIH CRM
NIAMS
NIH
50 South Drive
Bethesda, MD 20892
Email: mahendra.rao@nih.gov

Allan Robins, PHD
Acting CEO
Viacyte, Inc.
111 Riverbend Road
Athens, GA 30602
Tel: 706-613-9878 ext.158
Fax: 706-613-9879
Email: arobins@viacyte.com

Hannele Ruohola-Baker, PHD
University of Washington
815 Mercer Street
Seattle, WA 98109
Email: hannele@u.washington.edu

Tom Schulz
Associate Director of ES Cell Technology and Scale Up
Viacyte
111 Riverbend Road
Athens, GA 30602
Email: tschulz@viacyte.com

Deirdre Scripture-Adams, PHD
Research Biologist
MIMG, UCLA
UCLA Hematology Oncology BSRB
Room 18811
Attn: D. Scripture-Adams/ZACK
615 Charles E. Young Drive
Los Angeles, CA 90095-8348
Tel: 310-406-4799
Email: deirdre@ucla.edu

Bryce Seifert
Graduate Student
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, BCM 505
Alkek, N1020
Houston, TX 77030
Tel: 713-798-1273
Fax: 713-798-1230
Email: seifert@bcm.edu

Maria Sierra, PHD
Post-doctoral fellow
Molecular, Cell & Developmental Biology
UCLA
615 Charles E Young Drive South
BSRB 457
Los Angeles, CA 90095
Tel: 310-206-0620
Email: msierra@ucla.edu

Jiao Sima
Graduate-student
Biological Science
Florida State University
319 Stadium Drive
King Life Science Building, 3070
Tallahassee, FL 32306-4295
Tel: 850-980-1481
Email: jiao@bio.fsu.edu

Amar Singh, PHD
Post-doctoral Associate
Biochemistry
University of Georgia
500 DW Brooks Drive
Paul D. Coverdell Center, Room 276
Athens, GA 30602
Email: singha@uga.edu

Igor Slukvin, MD, PHD
University of Wisconsin
Stephen Smale, PHD
Professor
Microbiology, Immunology, and Molecular Genetics UCLA
6730 MRL, UCLA
675 Charles E. Young Drive South
Los Angeles, CA 90095-1662
Tel: 310-206-4777
Fax: 310-206-8623
Email: smale@mednet.ucla.edu

Lloyd Smith
University of Wisconsin
Zhou Songyang
Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Email: songyang@bcm.edu

Abdenour Soufi, PHD
Post-doctoral
Cell and Development Biology
University of Pennsylvania
1046 BRB II/III building
421 Curie Boulevard
Philadelphia, PA 19104-6058
Email: asoufi@upenn.edu

Kran Suknuntha, MD
University of Wisconsin
1220 Capitol Court
R 104
Madison, WI 53715
Tel: 608-335-8949
Email: suknuntha@wisc.edu

Michael Teitell, MD, PHD
Professor of Pathology and Laboratory Medicine,
Pediatrics
Pathology & Laboratory Medicine
University of California, Los Angeles
675 Charles E Young Drive S, 4-762 MRL
BOX 951732
Los Angeles, CA 90095
Tel: 310-825-9744
Fax: 310-267-0382
Email: mteitell@mednet.ucla.edu

James Thomson
Director of Regenerative Biology
Morgridge Institute for Research
330 N Orchard Street
Madison, WI 53715
Tel: 608-316-4348
Email: jthomson@morgridgeinstitute.org

Michael Tiemeyer, PHD
Complex Carbohydrate Research Center
University of Georgia
Complex Carbohydrate Research Center
University of Georgia
315 Riverbend Road
Athens, GA 30602
Tel: 706-542-2740
Fax: 706-542-4412
Email: mtiemeyer@ccrc.uga.edu

Hengbin Wang, PHD
Assistant Professor
Biochemistry and Molecular Genetics
University of Alabama at Birmingham
Kaul Human Genetics Building 402A
720 20th Street South
Birmingham, AL 35294
Tel: 205-934-5286
Fax: 205-934-0758
Email: hbwang@uab.edu

Qin Wang
Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Email: qmwang@bcm.edu

Sherman Weissman, MD
Professor
Genetics
Yale University School of Medicine
PO Box 208005
New Haven, CT 06520
Tel: 203-737-2281
Email: sherman.weissman@yale.edu

Lance Wells, PHD
Associate Professor
Complex Carbohydrate Research Center
University of Georgia
UGA, CCRC, 315 Riverbend Road
Athens, GA 30605
Tel: 706-202-8522
Fax: 706-542-4412
Email: lwells@ccrc.uga.edu

Korey Wilson
Graduate Student
Biology
Florida State University
1517 Mayhew Street
Tallahassee, FL 32304
Email: kwilson@bio.fsu.edu

Joseph Wu, MD, PHD
Associate Professor
Medicine
Stanford265 Campus Drive, G1120B
Stanford, CA 94306-5454
Tel: 650-736-2246
Fax: 650-736-0234
Email: joewu@stanford.edu

Young-Sup Yoon, MD, PHD
Emory University
101 Woodruff Circle
WMB 3309
Atlanta, GA 30345
Email: yyoon5@emory.edu

Pengzhi (Palmer) Yu, PHD
University of Wisconsin
330 North Orchard Street
Room 4316
Madison, WI 53715
Email: pyu2@wisc.edu

Jerome Zack, PHD
Professor
Medicine/MI&MG
UCLA
AIDS Institute
615 Charles E Young Drive South
BSRB 173
Los Angeles, CA 90095
Tel: 310 825 0876
Email: jzack@ucla.edu

Ken Zaret, PHD
Professor
Cell and Developmental Biology
University of Pennsylvania School of Medicine
Department of Cell and Developmental Biology
BRB II/III, Room 1056
Philadelphia, PA 19104
Tel: 215-573-5813
Fax: 215-746-8791
Email: zaret@upenn.edu

Marion Zatz, PHD
Program Director
Genetics and Developmental Biology
NIGMS/NIH
45 Center Drive, MSC 6200
Bethesda, MD 20892
Tel: 301-594-0943
Email: zatzm@nigms.nih.gov

Thomas Zwaka, MD
Associate Professor
Center for Cell and Gene Therapy
Baylor College of Medicine
One Baylor Plaza, BCM 505
Alkek, N1020
Houston, TX 77030
Tel: 713-798-1272
Fax: 713-798-1230
Email: tpzwaka@bcm.edu