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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Oct 18, 2013

 

One or more chief cells, which normally make digestive juices in the stomach,
have changed into a stem cell in the images above, filling its gland (outlined
by dashed lines) with green-tinted descendants. Scientists learned that
this change naturally occurs more often than they thought.







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Stomach cells naturally revert to stem cells

New research has shown that the stomach naturally produces more stem cells than previously realized, likely for repair of injuries from infections, digestive fluids and the foods we eat.

Stem cells can make multiple kinds of specialized cells, and scientists have been working for years to use that ability to repair injuries throughout the body. But causing specialized adult cells to revert to stem cells and work on repairs has been challenging.

Scientists from Washington University School of Medicine in St. Louis, and the Utrecht Medical Center in the Netherlands, report in a new study that a class of specialized cells in the stomach reverts to stem cells more often than they thought.


"We already knew that these cells, which are called chief cells, can change back into stem cells to make temporary repairs in significant stomach injuries, such as a cut or damage from infection.

"The fact that they're making this transition more often, even in the absence of noticeable injuries, suggests that it may be easier than we realized to make some types of mature, specialized adult cells revert to stem cells."

Jason Mills, MD, PhD, associate professor of medicine, Washington University


The findings are published Oct. 10 in Cell.

Chief cells normally produce digestive fluids for the stomach. Mills studies their transformation into stem cells for injury repair. He also is investigating the possibility that the potential for growth unleashed by this change may contribute to stomach cancers.

In the new report, Mills, graduate student Greg Sibbel and Hans Clevers, MD, PhD, a geneticist at Utrecht Medical Center, identify markers that show a small number of chief cells become stem cells even in the absence of serious injury.


If a significant injury is introduced in cell cultures or in animal models, more chief cells become stem cells, making it possible to fix the damage.


"Chief cells normally are big factories with elaborate networks of tubing and secretory mechanisms for making and secreting digestive juices," said Mills, the associate director of Washington University's Digestive Diseases Center. "That all has to be dismantled and recycled so the chief cell can become a stem cell. It's a remarkable change."

Mills' other goals include learning if the chief cells' transformations are triggered by signals sent by injured tissue, by damage sensors on the chief cells or by some combination of these methods.

Abstract Highlights
A subset of quiescent, differentiated chief cells express Troy
Troy+ chief cells can generate all differentiated lineages of the gastric epithelium
Troy+ chief cells act as “reserve” stem cells upon challenge of tissue homeostasis
Troy+ chief cells can initiate long-term in vitro cultures
Summary

Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bidirectionally toward pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent “reserve” stem cells. These observations challenge the notion that stem cell hierarchies represent a “one-way street.”

This research was supported by funding from the Centre for Biomedical Genetics, the European Research Council (EU-232814-StemCellMark, EU/Health-F4-2007-200720, DK09489, and 2P30 DK052574), the National Research Foundation of Korea (NRF2011-357-C00093), the Wellcome Trust (097922/C/11/Z), EU Marie Curie Fellowships (EU/236954-ICSC-Lgr5, and EU/300-686-InfO), and TI PHarma (T3-106).

Stange DE, Koo BK, Huch M, Sibbel G, Basak O, Lyubimova A, Kujala P, Bartfeldt S, Koster J, Geahlen JH, Peters PJ, van Ese JH, van de Wetering M, Mills JC, Clevers H. Differentiated Troy + chief cells act as 'reserve' stem cells to generate all lineages of the stomach epithelium. Cell, published online Oct. 10, 2013.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Original press releas:https://news.wustl.edu/news/Pages/25957.aspx