Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

Abstract

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

Differential sensitivity of gastric and small intestinal muscles to inducible knockdown of anoctamin 1 and the effects on gastrointestinal motility

“…The identity of the cation conductance is unknown, but deep sequencing of transcripts from adult cells identified expression of TRPM and TRPC family genes in small intestinal ICC (Lee et al . ). Additional experiments will be required to characterize the properties of the cation current in adult ICC, to learn how channels are gated during slow waves and to test the effects of knockouts of channel candidates on slow waves and small bowel motility behaviours.…”

The cells and conductance mediating cholinergic neurotransmission in the murine proximal stomach

“…; Lee et al . ) and translated to protein labelled by immunohistochemical techniques (Blair et al . ; Gomez‐Pinilla et al .…”

Extracellular Cl− regulates electrical slow waves and setting of smooth muscle membrane potential by interstitial cells of Cajal in mouse jejunum

“…; Lee et al . , ) reveals that RNA for CLCN voltage‐gated Cl − channels, two Cl − ‐transporting Slc4a anion exchangers (AE2 and AE3) and the KCC Slc12a cation‐coupled Cl − transporters as well as several members of the anoctamin/TMEM16 family of Ca 2+ ‐activated Cl − channels are expressed in smooth muscle cells (Lee et al . ).…”