Doublecortin-like kinase 1-positive enterocyte - a new cell type in human intestine.
Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell-like properties. The occurrence and pathological role of DCLK1-positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double-stained with DCLK1, and synaptophysin, chromogranin A and Ki-67. Ultrastructure of DCLK1-expressing duodenal cells was assessed using correlative light and electron microscopy. DCLK1 expression was seen in about 1% of epithelial cells diffusely scattered through the intestinal epithelium. Electron microscopy showed that the duodenal DCLK1-positive cells had short apical microvilli similar to neighbouring enterocytes and cytoplasmic granules on the basal side. DCLK1-positive cells were stained with synaptophysin. The number of DCLK1-positive cells was decreased in villus atrophy in coeliac disease. Our findings indicate that in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes, and their number is decreased in untreated coeliac disease.
Department of Pathology, University of Oulu, Oulu, Finland. joni.leppanen@oulu.fi.|Department of Surgery, University of Oulu, Oulu, Finland. joni.leppanen@oulu.fi.|Medical Research Center Oulu, Oulu, Finland. joni.leppanen@oulu.fi.|Oulu University Hospital, Oulu, Finland. joni.leppanen@oulu.fi.
Joni
J
Leppänen
Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
Olli
O
Helminen
Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
Heikki
H
Huhta
Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
Joonas H
JH
Kauppila
Biocenter Oulu, Oulu, Finland.
Ilkka
I
Miinalainen
Biocenter Oulu, Oulu, Finland.
Veli-Pekka
VP
Ronkainen
Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
Juha
J
Saarnio
Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.|Department of Anatomy and Cell biology, University of Oulu, Oulu, Finland.
Petri P
PP
Lehenkari
Department of Pathology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
Tuomo J
TJ
Karttunen
D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000473:pathology; D053379:Chromogranin A / Q000032:analysis; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D000089742:Doublecortin-Like Kinases; D004386:Duodenum / Q000166:cytology*; D020895:Enterocytes / Q000737:chemistry* / Q000145:classification* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology*; D007420:Intestine, Large / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D007583:Jejunum / Q000166:cytology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008853:Microscopy; D008871:Microvilli / Q000648:ultrastructure; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D016708:Synaptophysin / Q000032:analysis; D055815:Young Adult
C506150:CHGA protein, human; D053379:Chromogranin A; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C569014:SYP protein, human; D016708:Synaptophysin; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
Doublecortin-like kinase 1; duodenum; electron microscope; immunohistochemistry; synaptophysin