Identification of Newly Committed Pancreatic Cells in the Adult Mouse Pancreas

Abstract

Multipotent epithelial cells with high Aldehyde dehydrogenase activity have been previously reported to exist in the adult pancreas. However, whether they represent true progenitor cells remains controversial. In this study, we isolated and characterized cells with ALDH activity in the adult mouse or human pancreas during physiological conditions or injury. We found that cells with ALDH activity are abundant in the mouse pancreas during early postnatal growth, pregnancy, and in mouse models of pancreatitis and type 1 diabetes (T1D). Importantly, a similar population of cells is found abundantly in healthy children, or in patients with pancreatitis or T1D. We further demonstrate that cells with ALDH activity can commit to either endocrine or acinar lineages, and can be divided into four sub-populations based on CD90 and Ecadherin expression. Finally, our in vitro and in vivo studies show that the progeny of ALDH1+/CD90−/Ecad− cells residing in the adult mouse pancreas have the ability to initiate Pancreatic and duodenal homeobox (Pdx1) expression for the first time. In summary, we provide evidence for the existence of a sortable population of multipotent non-epithelial cells in the adult pancreas that can commit to the pancreatic lineage following proliferation and mesenchymal to epithelial transition (MET).

Conversion of α-Cells to β-Cells in the Postpartum Mouse Pancreas Involves Lgr5 Progeny

“…The enzymatic activity of ALDH allows isolation by FACS using a fluorogenic ALDH substrate known as Aldefluor. In a previous report, we showed that ALDHexpressing cells have the ability to differentiate into b-cells after parturition (36). We further demonstrated that the Alde 1 cells in the adult pancreas can be divided into four distinct subpopulations on the basis of E-cadherin and CD90 expression (36).…”

“…In a previous report, we showed that ALDHexpressing cells have the ability to differentiate into b-cells after parturition (36). We further demonstrated that the Alde 1 cells in the adult pancreas can be divided into four distinct subpopulations on the basis of E-cadherin and CD90 expression (36). Under normal conditions, the Alde population consists mainly of CD90 À cells; however, the percentage of mice having CD90 1 cells increases concomitantly with gestation during pregnancy and peaks toward the end of gestation when Alde 1 / CD90 1 cells can be found in 75-80% of dams (36).…”

“…Total mouse pancreas was used for isolation of duct and Aldefluor-positive (Alde 1 ) cells as previously described (36). The aldehyde dehydrogenase (ALDH) activity was detected using the ALDEFLUOR assay kit (STEMCELL Technologies) per the manufacturer's instructions.…”

In-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells

“…Here (Fig.6C), we show those IDs that appeared on t-SNE plots within a specific stage or cell subpopulation. While few of the IDs were expected based on literature search, we propose that Carboxypeptidase E (CPE,(71), MAN1A (Mannosidase Alpha Class 1A Member 1,(72), and ALDH1A1 (aldehyde dehydrogenase 1 family member A1, (73) deserve a further consideration for the modulation of differentiation protocol efficiency and developmental research. All other protein IDs from Fig.3C were not clearly identified or were at minimal detection levels at both t-SNE plots.…”

Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice

“…Recently, highly proliferative α-cell-like progenitors have also been described in the human pancreas throughout life, 48 as well as newly-committed endocrine progenitors in the mouse pancreas that selectively express high ALDH activity. 49 Either of these populations could be progenitors to Ins + Glut2 LO cells, or distinct progenitor pools that are amenable to HSC-induced expansion and differentiation to become functional β-cells. In summary, we showed that a single intrapancreatic injection of either MSC or HSC from mouse bone marrow can transiently improve glycemic control in diabetic mouse recipients, but with different time courses and likely different mechanisms of action.…”