mCCD_cl1 cells show plasticity consistent with the ability to transition between principal and intercalated cells

Area of Science:

• Nephrology
• Cell Biology
• Physiology

Background:

• The mammalian kidney's cortical collecting duct regulates body fluid and electrolyte balance.
• Principal and intercalated cells are the two main cell types, identified by specific protein markers like aquaporin 2 (Aqp2) and V-ATPase B1.
• The mCCDcl1 cell line is a common model for mouse principal cells.

Purpose of the Study:

• To investigate the cellular plasticity and lineage relationship of mCCDcl1 cells.
• To determine if single-cell clones of mCCDcl1 cells retain principal cell characteristics or exhibit mixed cell-type markers.

Main Methods:

• mCCDcl1 parental cells and three sublines (Ed1, Ed2, Ed3) were cultured on filters.
• Transepithelial electrical properties (resistance, voltage, current) were measured.
• Immunocytochemistry and RT-PCR were used to detect cell-specific markers (Aqp2, ENaC, V-ATPase B1, Cx30).

Main Results:

• The parental mCCDcl1 line showed principal cell function (sodium transport) but also expressed intercalated cell markers (V-ATPase B1, Cx30).
• Some cells in the parental line were positive for both principal (Aqp2, ENaC) and intercalated cell markers.
• All three subclonal lines contained cells expressing markers for both principal and intercalated cells.

Conclusions:

• mCCDcl1 cells demonstrate significant plasticity, interconverting between principal and intercalated cell phenotypes.
• Single-cell cloning reveals a potential precursor relationship between principal and intercalated cells within the mCCDcl1 line.
• These findings challenge the traditional view of distinct cell lineages and highlight the developmental flexibility in kidney collecting duct cells.