Kim, TH;
Saadatpour, A;
Guo, G;
Saxena, M;
Cavazza, A;
Desai, N;
Jadhav, U;
... Shivdasani, RA; + view all
(2016)
Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5(+) Intestinal Stem Cells.
Cell Reports
, 16
(8)
pp. 2053-2060.
10.1016/j.celrep.2016.07.056.
Preview |
Text
Kim et al, Cell Reports 2016.pdf - Published Version Download (9MB) | Preview |
Abstract
Lgr5(+) intestinal stem cells (ISCs) drive epithelial self-renewal, and their immediate progeny-intestinal bipotential progenitors-produce absorptive and secretory lineages via lateral inhibition. To define features of early transit from the ISC compartment, we used a microfluidics approach to measure selected stem- and lineage-specific transcripts in single Lgr5(+) cells. We identified two distinct cell populations, one that expresses known ISC markers and a second, abundant population that simultaneously expresses markers of stem and mature absorptive and secretory cells. Single-molecule mRNA in situ hybridization and immunofluorescence verified expression of lineage-restricted genes in a subset of Lgr5(+) cells in vivo. Transcriptional network analysis revealed that one group of Lgr5(+) cells arises from the other and displays characteristics expected of bipotential progenitors, including activation of Notch ligand and cell-cycle-inhibitor genes. These findings define the earliest steps in ISC differentiation and reveal multilineage gene priming as a fundamental property of the process.
Archive Staff Only
 |
View Item |
