Lifting the Mist on Gastric Stem Cells Julia Varga, Florian R. Greten  Cell Stem Cell  Volume 18, Issue 1, Pages 7-9 (January 2016) DOI: 10.1016/j.stem.2015.12.008 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Mist1+ Isthmus Cells Serve as Both Normal and Cancer Stem Cells and Are Supported by Wnt5a-Producing Cxcr4+ ILCs (A) Mist1+ isthmus cells reside in a specialized niche composed of Cxcl12+ endothelium and Cxcr4+ ILCs, which produce Wnt5a. Mist1+ stem cells are capable of generating all differentiated cell types in the corpus gland. (B) Mist1+ cells serve as cells-of-origin both for intestinal-type and diffuse-type gastric cancer. Concomitant Kras mutation and loss of Apc or Notch activation triggers intestinal metaplasia and intestinal-like gastric cancer. On the other hand loss of E-cadherin together with inflammation results in the formation of premalignant cells (signet ring cells) that progress into diffuse-type gastric cancer. Cxcr4+ ILCs are expanded in the cancer stem cell niche resulting in elevated levels of Wnt5a when compared to the normal stem cell niche. (C) Targeting the stem cell niche by a small-molecule Cxcr4 antagonist or by depleting ILCs provides a promising new therapeutic approach in diffuse-type gastric cancer. Cell Stem Cell 2016 18, 7-9DOI: (10.1016/j.stem.2015.12.008) Copyright © 2016 Elsevier Inc. Terms and Conditions