. 2017 Mar 6;4(1):89–94. doi: 10.1016/j.jcmgh.2017.02.009

Table 1.

Evidence for Cellular Origins of Metaplasia

	Evidence for chief cells	Evidence for Mist1⁺ isthmus stem cells
Proliferation	None in normal state, and minimal (<5%) in injury	Normally slow proliferation, and marked expansion in injury
BrdU labeling	No uptake in normal state, with rare labeling after injury (eg, 5-FU), but no upward migration⁸	Labeled cells migrate bidirectionally from the isthmus upward toward the pits and downward to the base
Lineage tracing	Troy-derived long-term tracing in haploinsufficient Troy knockin models,⁸ but not in Troy BAC models⁶ Chief cells express Lgr5, but no tracing from Lgr5⁺ chief cells in normal and injury states⁹; ablation of Lgr5⁺ chief cells does not decrease Mist1-derived tracing⁶ No evidence that chief cells expand clonally	Mist1-CreERT labels the isthmus stem cell as well as chief cells, and tracing arises from the isthmus stem cell⁶ 5-FU–induced stem cell ablation eliminates Mist1 tracing⁶ Confetti mice show clonal expansion from the isthmus⁶ eR1-CreERT mice show lineage tracing from the isthmus¹⁰
DMP-777	TFF2⁺IF⁺ cells present in lower third of glands after treatment, but morphology of these SPEM cells is atypical and changes are transient (<2 wk) DMP-777 reduces Mist1-traced chief cell number5, 6	Mist1⁺ isthmus stem cell–derived tracing is not altered after DMP-777⁶ Human gastric metaplasia is stable and clonal with a field effect, indicating stem cell origins³
Mutant Kras	Proliferating GS2⁺IF⁺ cells at the base after 1 month⁷ eR1-CreERT with Kras mutation leads to occasional GS2⁺ metaplasia near the gland base¹⁰ Most chief cells do not proliferate even after Kras induction at early time points, and are replaced rapidly by the migration of isthmus-derived SPEM cluster	Mucous-producing proliferating GS2/MUC6⁺ SPEM that is Alcian blue⁺ is present early on only in the isthmus Gland fission is present early only in the isthmus Lgr5-DTR–mediated ablation of chief cells does not reduce metaplasia, whereas suppression of the isthmus stem cell (with 5-FU) blocks metaplasia⁶ Metaplasia in eR1-CreERT;LSL-Kras mice starts primarily in the isthmus¹⁰

BrdU, bromodeoxyuridine; 5-FU, 5-fluorouracil.