Harvard stem cell scientists have a new theory for how stem cells decide whether to become liver or pancreatic cells during development. A cell's fate, the researchers found, is determined by the nearby presence of prostaglandin E2, a messenger molecule best known for its role in inflammation and pain. The discovery, published in the journal Developmental Cell, could potentially make liver and pancreas cells easier to generate both in the lab and for future cell therapies.
Wolfram Goessling, MD, PhD, and Trista North, PhD, both principal faculty members of the Harvard Stem Cell Institute (HSCI), identified a gradient of prostaglandin E2 in the region of zebrafish embryos where stem cells differentiate into the internal organs. Experiments conducted by postdoctoral fellow Sahar Nissim, MD, PhD, in the Goessling lab showed how liver-or-pancreas-fated stem cells have specific receptors on their membranes to detect the amount of prostaglandin E2 hormone present and coerce the cell into differentiating into a specific organ type.
"Cells that see more prostaglandin become liver and the cells that see less prostaglandin become pancreas," said Goessling, a Harvard Medical School Assistant Professor of Medicine at Brigham and Women's Hospital and Dana-Farber Cancer Institute. "This is the first time that prostaglandin is being reported as a factor that can lead this fate switch and essentially instruct what kind of identity a cell is going to be."
The researchers next collaborated with the laboratory of HSCI Affiliated Faculty member Richard Maas, MD, PhD, Director of the Genetics Division at Brigham and Women's Hospital, to see whether prostaglandin E2 has a similar function in mammals. Richard Sherwood, PhD, a former graduate student of HSCI Co-director Doug Melton, was successfully able to instruct mouse stem cells to become either liver or pancreas cells by exposing them to different amounts of the hormone. Other experiments showed that prostaglandin E2 could also enhance liver growth and regeneration of liver cells.
Goessling and his research partner North, a Harvard Medical School Assistant Professor of Pathology at Beth Israel Deaconess Hospital, first became intrigued by prostaglandin E2 in 2005, as postdoctoral fellows in the lab of HSCI Executive Committee Chair Leonard Zon, MD. It caught their attention during a chemical screen exposing 2,500 known drugs to zebrafish embryos to find any that could amplify blood stem cell populations. Prostaglandin E2 was the most successful hit -- the first molecule discovered in any system to have such an effect -- and recently successfully completed Phase 1b clinical trials as a therapeutic to improve cord blood transplants.
"Prostaglandin might be a master regulator of cell growth in different organs," Goessling said. "It's used in cord blood, as we have shown, it works in the liver, and who knows what other organs might be affected by it."
With evidence of how prostaglandin E2 works in the liver, the researchers next want to calibrate how it can be used in the laboratory to instruct induced pluripotent stem cells -- mature cells that have been reprogrammed into a stem-like state -- to become liver or pancreas cells. The scientists predict that such a protocol could benefit patients who need liver cells for transplantation or who have had organ injury.
Story Source:
The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.
Original post:
Scientists find cell fate switch that decides liver, or pancreas?
- International Stem Cell Corporation Provides Strategic Update on its Skin Care Program [Last Updated On: April 9th, 2010] [Originally Added On: April 9th, 2010]
- International Stem Cell Corporation Provides Strategic Update on its Skin Care Program [Last Updated On: April 9th, 2010] [Originally Added On: April 9th, 2010]
- CSC news roundup 2010-04-11 [Last Updated On: April 12th, 2010] [Originally Added On: April 12th, 2010]
- CSC news roundup 2010-04-11 [Last Updated On: April 12th, 2010] [Originally Added On: April 12th, 2010]
- International Stem Cell Corporation Engages Leading Immunogeneticists to Advance its Industry-first, Immune-matched Stem Cells [Last Updated On: April 14th, 2010] [Originally Added On: April 14th, 2010]
- International Stem Cell Corporation Engages Leading Immunogeneticists to Advance its Industry-first, Immune-matched Stem Cells [Last Updated On: April 14th, 2010] [Originally Added On: April 14th, 2010]
- MicroRNA therapy could be a powerful tool to correct the CSC dysregulation? [Last Updated On: April 17th, 2010] [Originally Added On: April 17th, 2010]
- MicroRNA therapy could be a powerful tool to correct the CSC dysregulation? [Last Updated On: April 17th, 2010] [Originally Added On: April 17th, 2010]
- CSC news links 2010-04-18 [Last Updated On: April 19th, 2010] [Originally Added On: April 19th, 2010]
- CSC news links 2010-04-18 [Last Updated On: April 19th, 2010] [Originally Added On: April 19th, 2010]
- Sessions on CSC Therapeutics at AACR10 [Last Updated On: April 27th, 2010] [Originally Added On: April 27th, 2010]
- Sessions on CSC Therapeutics at AACR10 [Last Updated On: April 27th, 2010] [Originally Added On: April 27th, 2010]
- CSC news links 2010-05-01 [Last Updated On: May 2nd, 2010] [Originally Added On: May 2nd, 2010]
- More about presentations at AACR10 [Last Updated On: May 2nd, 2010] [Originally Added On: May 2nd, 2010]
- More about presentations at AACR10 [Last Updated On: May 2nd, 2010] [Originally Added On: May 2nd, 2010]
- CSC news links 2010-05-01 [Last Updated On: May 2nd, 2010] [Originally Added On: May 2nd, 2010]
- International Stem Cell Corporation Signs Financing Agreement [Last Updated On: May 6th, 2010] [Originally Added On: May 6th, 2010]
- International Stem Cell Corporation Signs Financing Agreement [Last Updated On: May 6th, 2010] [Originally Added On: May 6th, 2010]
- CSC news links 2010-05-08 [Last Updated On: May 9th, 2010] [Originally Added On: May 9th, 2010]
- CSC news links 2010-05-08 [Last Updated On: May 9th, 2010] [Originally Added On: May 9th, 2010]
- International Stem Cell and Absorption Systems Confirm Results Showing Stem Cell Derived Corneal Tissue as an Alternative to Animals for Drug Testing [Last Updated On: May 12th, 2010] [Originally Added On: May 12th, 2010]
- International Stem Cell and Absorption Systems Confirm Results Showing Stem Cell Derived Corneal Tissue as an Alternative to Animals for Drug Testing [Last Updated On: May 12th, 2010] [Originally Added On: May 12th, 2010]
- Generic drug a potential treatment for glioblastoma? [Last Updated On: May 14th, 2010] [Originally Added On: May 14th, 2010]
- Generic drug a potential treatment for glioblastoma? [Last Updated On: May 14th, 2010] [Originally Added On: May 14th, 2010]
- US Patent: Isolation and use of solid tumor stem cells [Last Updated On: May 18th, 2010] [Originally Added On: May 18th, 2010]
- US Patent: Isolation and use of solid tumor stem cells [Last Updated On: May 18th, 2010] [Originally Added On: May 18th, 2010]
- International Stem Cell Corporation and The Automation Partnership Enter into Strategic Alliance to Automate Cornea Tissue Production [Last Updated On: May 19th, 2010] [Originally Added On: May 19th, 2010]
- International Stem Cell Corporation and The Automation Partnership Enter into Strategic Alliance to Automate Cornea Tissue Production [Last Updated On: May 19th, 2010] [Originally Added On: May 19th, 2010]
- An evolving concept of CSC in tumor biology [Last Updated On: May 21st, 2010] [Originally Added On: May 21st, 2010]
- An evolving concept of CSC in tumor biology [Last Updated On: May 21st, 2010] [Originally Added On: May 21st, 2010]
- International Stem Cell Corporation Moves International Cornea Development Program Forward [Last Updated On: May 26th, 2010] [Originally Added On: May 26th, 2010]
- International Stem Cell Corporation Moves International Cornea Development Program Forward [Last Updated On: May 26th, 2010] [Originally Added On: May 26th, 2010]
- Phase I clinical trial of ICT-107 [Last Updated On: June 3rd, 2010] [Originally Added On: June 3rd, 2010]
- Phase I clinical trial of ICT-107 [Last Updated On: June 3rd, 2010] [Originally Added On: June 3rd, 2010]
- CSCs responsible for metastasis identified [Last Updated On: June 6th, 2010] [Originally Added On: June 6th, 2010]
- CSCs responsible for metastasis identified [Last Updated On: June 6th, 2010] [Originally Added On: June 6th, 2010]
- International Stem Cell Corporation's Parthenogenetic Stem Cell Patent is Approved by the United States Patent and Trademark Office [Last Updated On: June 9th, 2010] [Originally Added On: June 9th, 2010]
- International Stem Cell Corporation's Parthenogenetic Stem Cell Patent is Approved by the United States Patent and Trademark Office [Last Updated On: June 9th, 2010] [Originally Added On: June 9th, 2010]
- International Stem Cell Corporation Announces Company Update Conference Call. ISCO Chairman Kenneth Aldrich to Discuss 'Status of the Company' [Last Updated On: June 10th, 2010] [Originally Added On: June 10th, 2010]
- International Stem Cell Corporation Announces Company Update Conference Call. ISCO Chairman Kenneth Aldrich to Discuss 'Status of the Company' [Last Updated On: June 10th, 2010] [Originally Added On: June 10th, 2010]
- Decitabine may target ovarian CSCs? [Last Updated On: June 14th, 2010] [Originally Added On: June 14th, 2010]
- Decitabine may target ovarian CSCs? [Last Updated On: June 14th, 2010] [Originally Added On: June 14th, 2010]
- New Article from North County Times - BIOTECH: International Stem Cell Clears Debt, Gets Patent [Last Updated On: June 17th, 2010] [Originally Added On: June 17th, 2010]
- New Article from North County Times - BIOTECH: International Stem Cell Clears Debt, Gets Patent [Last Updated On: June 17th, 2010] [Originally Added On: June 17th, 2010]
- Patent application: Levels of Oct1 as a method of identifying CSCs [Last Updated On: June 18th, 2010] [Originally Added On: June 18th, 2010]
- Patent application: Levels of Oct1 as a method of identifying CSCs [Last Updated On: June 18th, 2010] [Originally Added On: June 18th, 2010]
- OncoMed Has 'Wnt' in its Sails [Last Updated On: June 21st, 2010] [Originally Added On: June 21st, 2010]
- OncoMed Has 'Wnt' in its Sails [Last Updated On: June 21st, 2010] [Originally Added On: June 21st, 2010]
- International Stem Cell Corporation Names Charles J. Casamento to Board of Directors [Last Updated On: June 23rd, 2010] [Originally Added On: June 23rd, 2010]
- International Stem Cell Corporation Names Charles J. Casamento to Board of Directors [Last Updated On: June 23rd, 2010] [Originally Added On: June 23rd, 2010]
- International Stem Cell Corporation (ISCO.OB) Announces New Patent Issuance Under License Agreement [Last Updated On: June 25th, 2010] [Originally Added On: June 25th, 2010]
- International Stem Cell Corporation (ISCO.OB) Announces New Patent Issuance Under License Agreement [Last Updated On: June 25th, 2010] [Originally Added On: June 25th, 2010]
- California Health Institute Interviews Jeffrey Janus - CEO of Lifeline Cell Technology [Last Updated On: June 29th, 2010] [Originally Added On: June 29th, 2010]
- California Health Institute Interviews Jeffrey Janus - CEO of Lifeline Cell Technology [Last Updated On: June 29th, 2010] [Originally Added On: June 29th, 2010]
- International Stem Cell Corporation - Excerpt from Agora Financial's Breakthrough Technology Alert by Patrick Cox [Last Updated On: July 1st, 2010] [Originally Added On: July 1st, 2010]
- International Stem Cell Corporation - Excerpt from Agora Financial's Breakthrough Technology Alert by Patrick Cox [Last Updated On: July 1st, 2010] [Originally Added On: July 1st, 2010]
- Melanoma-initiating cells identified [Last Updated On: July 2nd, 2010] [Originally Added On: July 2nd, 2010]
- Melanoma-initiating cells identified [Last Updated On: July 2nd, 2010] [Originally Added On: July 2nd, 2010]
- International Stem Cell Corporation and Sankara Nethralaya Launch Collaboration to Develop Stem Cell-Based Treatment for Corneal Vision Impairment [Last Updated On: July 8th, 2010] [Originally Added On: July 8th, 2010]
- International Stem Cell Corporation and Sankara Nethralaya Launch Collaboration to Develop Stem Cell-Based Treatment for Corneal Vision Impairment [Last Updated On: July 8th, 2010] [Originally Added On: July 8th, 2010]
- Two recent OA articles [Last Updated On: July 12th, 2010] [Originally Added On: July 12th, 2010]
- Two recent OA articles [Last Updated On: July 12th, 2010] [Originally Added On: July 12th, 2010]
- Innovative Researcher Vlog [Last Updated On: July 16th, 2010] [Originally Added On: July 16th, 2010]
- Innovative Researcher Vlog [Last Updated On: July 16th, 2010] [Originally Added On: July 16th, 2010]
- More about salinomycin [Last Updated On: July 19th, 2010] [Originally Added On: July 19th, 2010]
- More about salinomycin [Last Updated On: July 19th, 2010] [Originally Added On: July 19th, 2010]
- International Stem Cell Corporation Plans $10 Million Financing Through European Subsidiary [Last Updated On: July 23rd, 2010] [Originally Added On: July 23rd, 2010]
- International Stem Cell Corporation Plans $10 Million Financing Through European Subsidiary [Last Updated On: July 23rd, 2010] [Originally Added On: July 23rd, 2010]
- Irradiating brain's stem cell niche [Last Updated On: July 26th, 2010] [Originally Added On: July 26th, 2010]
- Irradiating brain's stem cell niche [Last Updated On: July 26th, 2010] [Originally Added On: July 26th, 2010]
- Prostate CSCs sensitive to gamma-tocotrienol? [Last Updated On: July 27th, 2010] [Originally Added On: July 27th, 2010]
- Prostate CSCs sensitive to gamma-tocotrienol? [Last Updated On: July 27th, 2010] [Originally Added On: July 27th, 2010]
- Researchers Study CSCs as Therapeutic Targets for Mesothelioma [Last Updated On: July 28th, 2010] [Originally Added On: July 28th, 2010]
- Researchers Study CSCs as Therapeutic Targets for Mesothelioma [Last Updated On: July 28th, 2010] [Originally Added On: July 28th, 2010]
- International Stem Cell Corporation and Sristi Biosciences Enter Distribution Agreement for Lifeline Cell Technology's Brand of Human Cell Culture... [Last Updated On: July 29th, 2010] [Originally Added On: July 29th, 2010]
- Disagreement about melanoma CSCs [Last Updated On: July 29th, 2010] [Originally Added On: July 29th, 2010]
- International Stem Cell Corporation and Sristi Biosciences Enter Distribution Agreement for Lifeline Cell Technology's Brand of Human Cell Culture... [Last Updated On: July 29th, 2010] [Originally Added On: July 29th, 2010]
- Disagreement about melanoma CSCs [Last Updated On: July 29th, 2010] [Originally Added On: July 29th, 2010]
- Cell of origin for human prostate cancer [Last Updated On: August 1st, 2010] [Originally Added On: August 1st, 2010]
- Cell of origin for human prostate cancer [Last Updated On: August 1st, 2010] [Originally Added On: August 1st, 2010]