= Cellular differentiation
{wiki}
= Cell differentiation
{synonym}
<Cell differentiation> is the acquisition of a specialized <cell state>, involving changes in structure, function and <gene expression>. A <neuron> and a <red blood cell> illustrate different outcomes: signaling and <oxygen> transport. Different functions usually do not require a different inherited <DNA> sequence for each function. The shared-<genome> principle concerns nucleated precursors and most nucleated descendants: a mature mammalian <red blood cell> has lost its <cell nucleus> and <mitochondria>, so it is not an example of two mature <biological cells> both retaining the same nuclear <DNA>. <Biology 2e by Mary Ann Clark and others>[Biology 2e, §40.2, Red Blood Cells: specialization and absence of a nucleus and mitochondria at mammalian maturity]{ref}
The puzzle is how a shared set of <genes> supports different jobs. <Gene expression> changes which <RNA> and <proteins> a <biological cell> produces, and in what amounts. A <transcription factor> can regulate several <genes>; different combinations of regulators can interpret the same signal differently. Stable regulatory patterns can persist through the <cell cycle>, providing memory of developmental history. Specialization therefore usually changes use of inherited information, rather than replacing the <genome> wholesale. <Molecular Biology of the Cell, 4th edition by Bruce Alberts and others>[Alberts et al., The Molecular Genetic Mechanisms That Create Specialized Cell Types, subsections The Expression of a Set of Genes Can Be Coordinated by a Single Protein and Stable Patterns of Gene Expression Can Be Transmitted to Daughter Cells, and Summary]{ref}
\Image[/cell-differentiation-shared-genome-expression.png]
{title=Shared <genes>, different <gene expression> and specialized <cell states>}
{description=Original schematic with three invented <genes> H, A and B. Both nucleated <biological cells> retain all three <genes>; colored outputs indicate different illustrative expression patterns. These are not measured <RNA> or <protein> amounts, named real <genes>, or a claim that real <gene expression> is simply on or off. The separate mammalian <red blood cell> note marks an important limit to the shared nuclear <DNA> comparison.}
A small counting example separates sequence from activity. Suppose the same three toy <genes> are present in every nucleated <biological cell>, and independently assign each <gene> an on/off state. There are $2^3=8$ possible expression profiles with no <DNA> replacement. The figure shows only two: H and A on versus H and B on. Real <gene expression> is graded and coordinated, so this count illustrates possible descriptions, not a prediction of eight actual cell types. The interesting consequence is that a stable <cell state> can depend on how a shared record is used.
<Stem cells> combine self-renewal with production of differentiated descendants; <progenitor cells> generally have more restricted developmental options and renewal capacity. Neither term means that a <biological cell> must give rise to every cell type. <Terminal differentiation> denotes advanced specialization within a lineage, often accompanied by exit from the <cell cycle>. <Cell fate> concerns the developmental outcome of a <biological cell> or its descendants, whereas <cell state> describes its current properties. A temporary change in <gene expression> after <signal transduction> is not, by itself, proof of a new <cell fate>. <Anatomy and Physiology 2e by J. Gordon Betts and others>[Anatomy and Physiology 2e, §3.6, Stem Cells and Differentiation: renewal, restricted differentiation potential and regulation of gene expression]{ref}
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