Collaboration Paper: Converting Adult Pancreatic Islet α Cells into β Cells by Dnmt1-Arx

Restoration of lost or diseased cells is a focus for intensive efforts in developmental and regenerative biology. Pancreatic islets are a paradigm for investigating organ restoration, reflecting growth in our understanding of the development and maturation by the principal islet cell types (which include insulin-producing β cells, glucagon-producing α cells, and somatostatin-producing δ cells). Understanding the mechanisms maintaining islet cell fate and function is important for addressing the urgent challenge of restoring islet β cell and α cell function, which is compromised in diseases like type 1 diabetes (T1D). Prior studies have demonstrated that mouse α cells or δ cells can convert into insulin-producing cells following extreme experimental (>99%) β cell ablation; in the case of α cells, about 1% convert toward an insulin-producing fate, without detectable proliferation over a period of 6–7 months (Thorel et al., 2010, Chera et al., 2014). However, the genetic or epigenetic basis of this conversion, including the extent or heterogeneity of reprogramming by individual adult α cells, has not been elucidated.

Chakravarthy et al. dissect the mechanisms maintaining α cell identity and reveal that simultaneous inactivation of the DNA methyltransferase Dnmt1 and the transcription factor Arx in adult mice drives the conversion of α- to β-like cells. In human T1D islets, glucagon+ cells lose DNMT1 and ARX expression and express β cell markers.

Continue your reading  here:

Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx

Authors: Harini Chakravarthy, Xueying Gu, Martin Enge, Xiaoqing Dai, Yong Wang, Nicolas Damond, Carolina Downie, Kathy Liu, Jing Wang, Yuan Xing, Simona Chera, Fabrizio Thorel, Stephen Quake, Jose Oberholzer, Patrick E. MacDonald, Pedro L. Herrera, Seung K. Kim
Journal: Cell Metabolism  (2017), Mar 7;25(3):622-634. PMID:28215845

DOI information:

Leave a Reply

Your email address will not be published. Required fields are marked *