Our biomedical knowledge-base consists of more than a century of publications using human cell lines. Cell culture terminology has inevitably changed over time. Terms used to describe a cell line and its progeny include “cell strain” , “cell lineage” , “children” , “clonal population”, and “cell population”.
For FIND Cell, we chose unifying terminologies that we consider to be most amenable to current trends in molecular biology. This does not mean we reject terminologies that have been chosen carefully by our colleagues.
A cell line is derived from a blood or tissue sample from a single patient with a unique genetic make-up. Such a sample is used to establish a primary culture. Once the primary culture is successfully passaged (sub-cultured), it becomes a cell line. Some cell lines have a finite lifespan, reaching senescence after a number of cell doublings. Other cell lines can be cultured continuously due to spontaneous or induced transformation to an immortal state.
Cell line genetics
A cell line has a unique genetic make-up that represents the patient it was derived from.
DNA-based cell line authentication ensures you are working with cells from that specific patient. The process involves matching a current DNA profile to a verified reference DNA profile in a database.
If multiple cell lines are established from different tissues of the same patient (e.g. blood, colon, kidney) – DNA-based cell line authentication will point out that each cell line was derived from that same patient.
Cell population refers to the group of cells in a specific culture vessel (e.g., a Petri dish) at a particular time point. “Population” is used because these cells can be heterogeneous in their genetic makeup and behavior.
Cell lineage or cell strain?
The terms cell lineage and cell strain are highly similar. The term “strain” is used in human cell culture, yeast genetics, and mouse genetics, among others, and often indicates a changed characteristic compared to the original cell line. In contrast, the term cell lineage is used more frequently in an in vivo context, such as in developmental biology, stem cell biology, hematology, and evolutionary studies in yeast and bacteria. It is used to describe the asexual inheritance of traits through cell doubling in a changing environment. It gives the notion of a continuum.
FIND Cell focuses on the process of cell culturing and not on single events.
Cell culture is similarly a continuum – it involves cascades of cell passaging, manipulation, selection, isolation, treatment, and freeze/thaw cycles. Once a cell lineage is established (after a gene edit, for example) and validated, you can rename it to indicate the change (or you can even call it a strain). But FIND Cell considers the continuum and therefore adopts cell lineage as the chosen term.
Cell lineage genetics
DNA-based cell line authentication ensures that the cell lineage you work with belongs to the expected ancestral cell line.
Cell lineages from the same cell line have a shared genetic origin, so DNA-based cell line authentication will identify them all as the same ‘cell line’.
Please note: a genetically modified cell lineage is sometimes indicated in databases as ‘a new cell line’ with a new name. Be aware that the DNA identification profile will still correspond to the original, ancestral cell line. Cellosaurus solved this by referring to these cell lineages as “children” of the original cell line.
Using genetic stability analysis, you can verify if the cell lineage drifted (or evolved) away from the ancestral cell line upon establishment (at passage 1 if verified at that time point).
A new lineage
If a cell culture has reached confluence, and you passage and split a subset of these cells into two physically separate culture vessels, then you start two new lineage branches. The lineages will independently evolve during ongoing sub-culturing. (see figure)
Isolation of a cell to establish a mono-clonal lineage introduces a “genetic bottleneck”, removing genetic heterogeneity that was present in the ancestral cell population (see figure). It is critically important to characterize if the overall phenotype of this monoclonal lineage has changed.
Sharing an aliquot of cells with a neighboring laboratory means giving your colleagues a specific lineage that has branched off from your cell lineage. This lineage will start its own evolutionary journey. A 2018 study showed that breast cancer-derived cell lineages (MCF-7) from 27 independent laboratories exhibited distinct genotypic and phenotypic traits when compared to one another .
Modern researchers can perform complex experiments, and with the described terminology we help them to keep track of the cell line continuum.
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Written by: Amanda Capes-Davis PhD, Tyler Joseph, and Sophie Zaaijer PhD
Illustrations: Kate White
Key references :
Schaeffer WI. Terminology associated with cell, tissue, and organ culture, molecular biology, and molecular genetics. Tissue Culture Association Terminology Committee. In Vitro Cell Dev Biol. 1990;26: 97–101.
#strain versus lineage