Table 1.

Immunology and neurobiology examples of class and modern cell identity definitions

Identifier category	Immune cells			Neural cells			Notes on identifiers**
	Feature(s)	Cell	Proof type	Feature(s)	Cell	Proof type	Pros	Cons
Morphology and location	Star shaped	Dendritic cells	Functional	Star shaped	Astrocytes	Functional [50]	Easily visualized	Not connected to specific molecules or functions
	-	-	-	Large, extensive dendritic tree; located in cerebellum	Purkinje neurons	Functional [51]
	-	-	-	Elongated radial shape, apical membrane contacting lateral ventricle SVZ	Adult neural stem cells	Functional [52, 53]
	-	-	-	Columnar shaped, multiciliated cells that line the ventricles	Ependymal cells	Functional [54]
Surface protein, extracellular epitope	CD3 +	T lymphocytes	Definitional, functional [42]	E-cadherin + , CD133, CD24	Ependymal cells	Strong evidence of epithelial barrier function [55–57]	Can be used to physically isolate live cells	Many surface proteins are not cell type restricted or have unknown functions
	CD19 +	B lymphocytes	Definitional, functional [58]	CD133, CD15, CD24, CD184	Adult neural stem cell	Strong evidence, not definitional, requires validation [59, 60]
	CD45 +	Mature, hematopoietic	Good evidence [41]	CD24, CD44	Astrocytes	Strong evidence, not definitional, requires validation [61]
	CD33 + CD16 + CD14-	Non-classical monocyte	Definitional [56]	CD140a (PDGFRa), NG2	Oligodendrocytes	Strong evidence, not definitional, requires validation [57, 62]
Transcription factor protein	FOXP3 +	Regulatory T cell (Treg)	Strong evidence, functional[43]	SOX2, PAX6	Adult neural stem cells	Strong evidence, but functional assays required [63, 64]	Transcription factors can directly change cell identity	Low expression levels, intracellular
	PAX5 +	Early B lymphocytes	Definitional, functional[44, 45, 65]	OLIG2, SOX10	Oligodendrocytes	Strong evidence, but functional assays required [62]
	BCL6 +	Germinal center B cell	Definitional, functional (in tissue context) [46]	NEUROD1	Neurons	Strong evidence, but functional assays required [66]
Other intracellular protein	CD20	B lymphocyte	Strong evidence [67]	TUJ1 (β-III-tubulin)	Neurons	Strong evidence (in tissue context) [68]	Commonly available	Low expression levels, intracellular
	LYN	B lymphocyte	Good evidence, functional [69]	MBP	Oligodendrocytes	Strong evidence (in tissue context) [70]
	TdT	(pre-B cells)	Definitional, functional [71]	GFAP, S100B	Astrocytes	Strong evidence (in tissue context) [72]
Protein production	Secretes IL-4	Th2 Helper T cell	Functional [73]	Produces myelin	Oligodendrocytes	Definitional, functional [70]	Functional test	Requires live cells, difficult assay, can require Golgi blocking agents
	Secretes immunoglobulin	Plasma cell	Definitional, functional [74]	Secretes neurotransmitters	Neurons	Definitional, functional [75]
	Secretes iNOS	Myeloid derived suppressor cell	Functional [76]	-	-	-
Intracellular feature	Engulfs bacteria, beads, or other cells	Phagocyte	Definitional, functional [39]	Electrical activity	Neurons	Definitional, functional [54]	Widely used	Requires live cells or tissue
Cell mixing assay	Suppresses T cell proliferation	Myeloid derived suppressor cell	Definitional, functional [38]	Oligodendrocyte and neuron co-culture to assess myelination	Oligodendrocytes	Definitional, functional [77, 78]	Commonly available	Requires cell culture and expertise
Lineage tracing assay	Produces all lymphocytes, no myeloid cells	Common lymphocyte progenitor	Definitional, functional [79]	Generates astrocytes, neurons and oligodendrocytes	Adult neural stem cells	Definitional, functional [80]	Commonly available	Requires animal model and/or live cells
DNA mutations	Somatic hypermutation in IgH gene	Antigen-experienced, mature B cells	Definitional, functional [81]	-	-	-	Commonly available	Low expression levels; not functional
Transcription factor mRNA	Surrogate, requires validation			Surrogate, requires validation			Commonly available	Low expression levels; not functional

^* Definitions may have exceptions in less commonly studied tissues or in the context of diseases. ** Other terms that do not mark cell identities (and explanation): stromal (in epithelial biology it marks a layer containing multiple cell types, in cancer it means "all other cell types'), mesenchymal (adjective applied to distinct types of cells, including adult cells of epithelial or hematopoietic origin), glial (typically denotes cells derived from a neural stem cell that are not neuronal, such as astrocytes and oligodendrocytes; historically denotes cells in nervous tissue that are not neurons), immune (marks a function seen on epithelial and hematopoietic cells), antigen presenting cell (marks a function, not a cell type)