Formalize the theory of cell types and states from the folk perspective

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Based on the common use of terms like:

• cell type
• cell state
• cell stage
• subtypes
• terminally differentiated cell
• multipotent, totipotent cell,
• undifferentiated cell
• transdifferentiation

How this concepts play out for a single individual?

In the zygote, there would be information encoding for a somewhat fixed number of terminally differentiated cell types

Corner cases:

• lymphocytes and VDJ recombination

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Some axioms:

• All human cells in any human come from a single zygote.

• The genome encodes a blueprint for a finite number of cell types, but an infinite number of cells

• Each cell is either in a transitional state or a terminally differentiated state .

• The terminally differentiated stated is what we usually refer to as cell type.

• A terminally differentiated cell can be assigned to one (and only one) genome-encoded cell type.

• This cell type is determined by a core Gene Expression Program (GEP), triggered by key transcription factors.

• Each terminally differentiated cell may also express a variety of other GEPs, also genome encoded. They do not change the cell type, and they are, at least in theory, temporary. The cell doesn't lose its identity if this GEP is lost.

• The overlay of a cell type and the currently present additional GEPs form a cell state, of the type that is observed in single-cell transcriptomic.

• Cells can enter a number of diseased states, where the additional GEPs are somehow linked to a loss of fitness/survival ability for the organism.

• Senescent cells are mature cells that started expressing GEPs related to senescence.

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• Potency is a cell ability to naturally differentiate into a range of terminally differentiated states (https://en.wikipedia.org/wiki/Cell_potency#Pluripotency)

• The zygote is a totipotent cell, as it can access all of the genome-encoded cell types.

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• There are intermediate stable transitional states, which also can be considered types. Cells in those states need type checkpoint signals to start a transition towards a stable state. Stem/precursor and progenitor cells can be considered to be in intermediate stable transitional states, or stem/progenitor/precursor cell types.

  • Example: Oligodendrocyte progenitor cell. (https://en.wikipedia.org/wiki/Oligodendrocyte_progenitor_cell)

• Cells that play the role of stem/progenitor/precursor cell types may also express additional GEPs and form cell states.

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• A cell of a terminally differentiated cell type may not become a different terminally differentiated cell types in nature. (i.e. there is no natural transdifferentiation of human cells).

• Cells may be differentiated (and transdifferentiated artificially), losing their natural types.

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• A cell subtype is a terminally differentiated state that is formed by a core GEP alongside minor permanent GEPs. They are also encoded by the genome and finite in number.

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• There is a core set of terminally differentiated states that are present in all humans. GEPs will have genomic variations, but there is no major qualitative change in the nature of these core cell types among different humans.

• These core set of terminally differentiated states might be found in any human.

• An exception is the sex-specific cell types that will be present or not, depending on the biological sex.

• Some cell types might be present only in particular human subpopulations.

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Idea:

• Generate a Google Forms with a Likert scale to see if researchers agree with the axioms.

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https://docs.google.com/forms/d/1-cZwKHAfslx0lHAzSP_0f1zBo5WKc1kReRF8bk4kZOA

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Maybe visualize using a radar plot