A methodological approach to tracing cell lineage in human epithelial tissues

Area of Science:

• Cell Biology
• Genetics
• Histology

Background:

• Lineage tracing of stem cell progeny in human tissues is challenging.
• Mitochondrial DNA (mtDNA) mutations can accumulate over time and affect cellular function.

Purpose of the Study:

• To develop and validate a novel method for lineage tracing of stem cell progeny in human tissues.
• To identify the location of stem cell niches in various human organs.
• To analyze the origin of human tumors.

Main Methods:

• Utilizing clonal mitochondrial DNA (mtDNA) mutations affecting cytochrome c oxidase (COX) expression.
• Employing dual-color enzyme histochemistry to detect COX-deficient cells.
• Confirming mutations via microdissection of single cells and polymerase chain reaction sequencing of the entire mtDNA genome.

Main Results:

• Identified stem cell niches in the colon, small intestine, pancreas, liver, and skin.
• Located stem cell niches at the base of colonic crypts, above Paneth cells in the small intestine, near interlobular ducts in the pancreas, and in the periportal region of the liver.
• Suggested the outer root sheath of hair follicles as the origin of basal cell carcinoma.

Conclusions:

• The described technique provides a general method for detecting clonal cell populations in human tissues.
• This method allows for the inference of stem cell niche locations and the generation of cell fate maps.
• The technique is valuable for analyzing the origin of human tumors from specific tissue sites.