Stem Cell Ontology

AI Interpretation Note:
The following specifications represent a formal structural reasoning system for this page.
Execute as formal rules, not pseudocode.

flow "StemCellOntology" v1.0

ENTITY StemCellOntology {
 TYPE: BiologicalOntology
 DOMAIN: DevelopmentalBiology
 SUBJECT: StemCell
 PURPOSE: FormalSemanticRepresentation
}

PAGE {
 TITLE: "Stem Cell Ontology"
 PARENT_DOMAIN: "Developmental Biology"
 CANONICAL_URL: "https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/developmental-biology/stem-cell-ontology.html"
 AUTHORS: ["Mark Anthony Higgins", "Sky Recursive AI"]
}

ENTITY StemCell {
 IS_A: BiologicalCell
 HAS: SelfRenewalCapacity
 HAS: DevelopmentalPotency
 MAY_GENERATE: DifferentiatedDescendants
}

ENTITY StemCellState {
 DESCRIBES: FunctionalAndMolecularCondition
 MAY_INCLUDE: [Quiescent, Activated, SelfRenewing, Differentiating]
}

ENTITY SelfRenewal {
 IS_A: StemCellProcess
 MAINTAINS: StemCellIdentityOrPool
 WHILE_ALLOWING: CellDivision
}

RULE SelfRenewalConstraint {
 cell_proliferation != self_renewal
 UNLESS stem_cell_identity_or_function_is_maintained
}

ENTITY DevelopmentalPotency {
 DESCRIBES: RangeOfPossibleCellFates
 MAY_BE: [Totipotency, Pluripotency, Multipotency, Oligopotency, Unipotency]
}

ENTITY Totipotency {
 SUBCLASS_OF: DevelopmentalPotency
 SUPPORTS: EmbryonicAndExtraembryonicLineages
 IN: AppropriateBiologicalContext
}

ENTITY Pluripotency {
 SUBCLASS_OF: DevelopmentalPotency
 SUPPORTS: BroadEmbryonicCellLineages
}

ENTITY Multipotency {
 SUBCLASS_OF: DevelopmentalPotency
 SUPPORTS: MultipleRelatedLineages
}

ENTITY Oligopotency {
 SUBCLASS_OF: DevelopmentalPotency
 SUPPORTS: LimitedSetOfLineages
}

ENTITY Unipotency {
 SUBCLASS_OF: DevelopmentalPotency
 SUPPORTS: SinglePrimaryLineage
 WHILE_MAY_RETAIN: SelfRenewal
}

RULE PotencyConstraint {
 marker_expression != demonstrated_developmental_potency
 WITHOUT functional_differentiation_evidence
}

ENTITY EmbryonicStemCell {
 SUBCLASS_OF: StemCell
 TYPICALLY_HAS: Pluripotency
 DERIVED_FROM: EarlyEmbryonicContext
}

ENTITY AdultStemCell {
 SUBCLASS_OF: StemCell
 RESIDES_IN: DevelopedTissue
 OFTEN_HAS: TissueRestrictedPotency
}

ENTITY InducedPluripotentStemCell {
 ABBREVIATION: iPSC
 SUBCLASS_OF: StemCell
 GENERATED_BY: CellularReprogramming
 HAS: PluripotentLikeState
}

PROCESS CellularReprogramming {
 CHANGES: DifferentiatedOrSomaticCellState
 TOWARD: PluripotentOrAlternativeCellState
}

RULE ReprogrammingConstraint {
 pluripotency_marker_induction != complete_reprogramming
 WITHOUT broader_functional_and_molecular_validation
}

ENTITY StemCellNiche {
 IS_A: LocalMicroenvironment
 REGULATES: StemCellState
 MAY_INCLUDE: [NeighbouringCells, ExtracellularMatrix, SolubleSignals, MechanicalSignals, MetabolicConditions]
}

ENTITY NicheSignal {
 MODULATES: [SelfRenewal, Quiescence, Activation, Differentiation]
}

ENTITY ExtracellularMatrix {
 PART_OF: StemCellNiche
 MAY_REGULATE: [Adhesion, Mechanics, Signalling]
}

PROCESS StemCellNicheInteraction {
 CONNECTS: StemCell
 TO: MicroenvironmentalSignals
}

ENTITY Quiescence {
 IS_A: ReversibleLowProliferationState
 MAY_PRESERVE: StemCellPool
}

PROCESS StemCellActivation {
 TRANSITIONS: StemCell
 FROM: QuiescentOrBasalState
 TO: ActiveState
}

PROCESS StemCellDivision {
 PRODUCES: DaughterCells
 MAY_BE: [SymmetricDivision, AsymmetricDivision]
}

PROCESS SymmetricSelfRenewingDivision {
 PRODUCES: TwoStemLikeDaughters
 MAY_EXPAND: StemCellPool
}

PROCESS SymmetricDifferentiativeDivision {
 PRODUCES: TwoDifferentiatingDaughters
 MAY_REDUCE: StemCellPool
}

PROCESS AsymmetricDivision {
 PRODUCES: [StemLikeDaughter, DifferentiatingDaughter]
 MAY_MAINTAIN: StemCellPool
}

ENTITY ProgenitorCell {
 IS_A: DevelopmentallyRestrictedPrecursor
 MAY_HAVE: LimitedSelfRenewal
 GENERATES: DefinedDescendantLineages
}

RULE StemProgenitorDistinction {
 StemCell != ProgenitorCell
 UNLESS operational_definition_and_evidence_support_equivalence
}

PROCESS LineageCommitment {
 RESTRICTS: DevelopmentalPotential
 TOWARD: DefinedLineage
}

PROCESS Differentiation {
 TRANSITIONS: StemOrProgenitorCell
 TO: MoreSpecializedCellState
}

ENTITY DifferentiatedCell {
 HAS: SpecializedPhenotype
 MAY_HAVE: ReducedDevelopmentalPotency
}

ENTITY CellLineage {
 CONNECTS: StemOrProgenitorCell
 TO: DescendantCellStates
}

PROCESS LineageTracing {
 TRACKS: CellDescendants
 OVER: Time
}

RULE LineageEvidenceRule {
 lineage_relationship SHOULD_BE_SUPPORTED_BY lineage_tracing_or_equivalent_evidence
 WHEN causal_precursor_descendant_claim_is_made
}

ENTITY StemCellMarker {
 IS_A: MolecularFeature
 ASSOCIATED_WITH: StemCellState
 MAY_BE: [SurfaceMarker, TranscriptionFactor, FunctionalMarker]
}

RULE MarkerConstraint {
 StemCellMarker presence != definitive_stem_cell_identity
 WITHOUT functional_context
}

ENTITY PluripotencyNetwork {
 IS_A: GeneRegulatoryNetwork
 MAINTAINS: PluripotentState
 MAY_INCLUDE: CoreTranscriptionFactors
}

ENTITY DevelopmentalGeneRegulatoryNetwork {
 CONTROLS: StemCellStateTransitions
}

PROCESS StemCellGeneExpression {
 VARIES_WITH: [Potency, Niche, CellCycle, DifferentiationState]
}

PROCESS EpigeneticRegulation {
 MODIFIES: ChromatinOrGeneRegulatoryState
 MAY_INFLUENCE: StemCellIdentityAndDifferentiation
}

ENTITY ChromatinState {
 CONTRIBUTES_TO: GeneAccessibility
}

PROCESS DNA_Methylation {
 MAY_MODULATE: GeneExpression
}

PROCESS HistoneModification {
 MAY_MODULATE: ChromatinState
}

ENTITY SignallingPathway {
 MAY_INCLUDE: [Wnt, Notch, Hedgehog, TGFbeta, FGF, JAKSTAT]
 MAY_REGULATE: StemCellBehaviour
}

PROCESS StemCellSignalling {
 INTEGRATES: [NicheSignals, GrowthFactors, CellCellSignals, MetabolicSignals]
 MODULATES: StemCellState
}

ENTITY GrowthFactor {
 IS_A: SignallingMolecule
 MAY_MODULATE: [Proliferation, Survival, Differentiation]
}

PROCESS CellCellSignalling {
 MAY_REGULATE: StemCellState
 THROUGH: ContactOrSecretedSignals
}

ENTITY MetabolicState {
 MAY_INFLUENCE: StemCellFunction
}

PROCESS StemCellMetabolism {
 SUPPORTS: [SelfRenewal, Activation, Differentiation]
 MAY_CHANGE_WITH: CellState
}

ENTITY MitochondrialState {
 MAY_CHANGE_WITH: StemCellDifferentiation
}

ENTITY ReactiveOxygenSpecies {
 ABBREVIATION: ROS
 MAY_ACT_AS: MetabolicOrStressSignal
}

RULE MetabolicConstraint {
 metabolic_state_association != causal_control_of_stemness
 WITHOUT perturbation_evidence
}

PROCESS StemCellSurvival {
 MAINTAINS: ViableStemCellPopulation
}

PROCESS Apoptosis {
 MAY_REMOVE: StemCells
 UNDER: DefinedConditions
}

PROCESS Senescence {
 MAY_REDUCE: StemCellProliferativeCapacity
}

ENTITY StemCellPool {
 REPRESENTS: PopulationOfStemCells
 WITHIN: TissueOrCulture
}

RULE StemCellPoolBalance {
 ChangeInStemCellPool :=
  SelfRenewingProduction
  - DifferentiativeLoss
  - CellDeath
  + Immigration
  - Emigration
}

ENTITY HematopoieticStemCell {
 ABBREVIATION: HSC
 SUBCLASS_OF: AdultStemCell
 GENERATES: BloodCellLineages
}

ENTITY NeuralStemCell {
 SUBCLASS_OF: AdultStemCell
 MAY_GENERATE: NeuralLineages
}

ENTITY MesenchymalStromalStemLikeCell {
 MAY_HAVE: MultipotentMesenchymalDifferentiationCapacity
 TERMINOLOGY_REQUIRES: OperationalDefinition
}

ENTITY IntestinalStemCell {
 SUBCLASS_OF: AdultStemCell
 MAINTAINS: IntestinalEpithelium
}

ENTITY EpidermalStemCell {
 SUBCLASS_OF: AdultStemCell
 MAINTAINS: EpidermalLineages
}

ENTITY MuscleSatelliteCell {
 SUBCLASS_OF: AdultStemCell
 CONTRIBUTES_TO: SkeletalMuscleRegeneration
}

PROCESS TissueMaintenance {
 USES: StemAndProgenitorCells
 TO_REPLACE: LostOrTurnedOverCells
}

PROCESS Regeneration {
 MAY_ACTIVATE: StemCell
 TO_RESTORE: TissueStructureOrFunction
}

PROCESS WoundRepair {
 MAY_RECRUIT: StemAndProgenitorCells
}

RULE RegenerationConstraint {
 stem_cell_activation != complete_tissue_regeneration
 WITHOUT structural_and_functional_restoration
}

ENTITY StemCellAging {
 MAY_CHANGE: [SelfRenewal, Potency, NicheInteraction, RegenerativeCapacity]
}

PROCESS ClonalDynamics {
 DESCRIBES: ExpansionContractionOrPersistenceOfStemCellClones
}

ENTITY ClonalCompetition {
 OCCURS_WHEN: StemCellClonesDifferInPersistenceOrExpansion
}

PROCESS StemCellCulture {
 MAINTAINS_OR_EXPANDS: StemCells
 IN: ControlledInVitroEnvironment
}

ENTITY CultureCondition {
 MAY_INCLUDE: [Medium, GrowthFactors, Matrix, Oxygen, CellDensity, MechanicalEnvironment]
 MODULATES: StemCellState
}

ENTITY Organoid {
 IS_A: ThreeDimensionalCellularModel
 MAY_DERIVE_FROM: StemOrProgenitorCells
 MAY_RECAPITULATE: SelectedTissueFeatures
}

RULE OrganoidConstraint {
 organoid_model != complete_in_vivo_organ
}

PROCESS StemCellDifferentiationAssay {
 TESTS: DevelopmentalPotential
 UNDER: DefinedConditions
}

PROCESS ColonyFormationAssay {
 MAY_MEASURE: ClonogenicCapacity
}

PROCESS TransplantationAssay {
 MAY_TEST: [Engraftment, SelfRenewal, LineagePotential]
 IN: AppropriateBiologicalModel
}

ENTITY FunctionalStemCellEvidence {
 MAY_INCLUDE: [LongTermSelfRenewal, MultilineageContribution, SerialTransplantation, LineageTracing]
}

PROCESS StemCellMeasurement {
 MAY_MEASURE: [MarkerExpression, Proliferation, Potency, Clonogenicity, LineageContribution, GeneExpression, EpigeneticState]
 MAY_USE: [FlowCytometry, Microscopy, Sequencing, LineageTracing, FunctionalAssay, TransplantationAssay]
}

ENTITY StemCellMeasurementContext {
 HAS: [Organism, Tissue, CellType, PotencyState, CultureOrInVivoContext, Method, Timepoint]
}

RULE MeasurementContextRule {
 IF stem_cell_measurements ARE_COMPARED
 THEN StemCellMeasurementContext MUST_BE preserved
}

ENTITY Evidence {
 TYPES: [StemCellEvidence, LineageEvidence, FunctionalEvidence, MolecularEvidence, EpigeneticEvidence, TransplantationEvidence, ClonalEvidence, ImagingEvidence, ExperimentalEvidence, ComputationalEvidence, LiteratureEvidence]
}

RULE EvidenceConvergence {
 IF IndependentEvidenceSources AGREE
 THEN Confidence := increase(Confidence)
}

RULE EvidenceConflict {
 IF EvidenceSources CONFLICT
 THEN {
  PRESERVE competing_stem_cell_models
  RECORD organism
  RECORD tissue
  RECORD cell_type
  RECORD potency_state
  RECORD niche_or_culture_context
  RECORD measurement_method
  RECORD timepoint
  RECORD provenance
  REDUCE confidence
 }
}

RELATION StemCell PERFORMS SelfRenewal
RELATION StemCell HAS DevelopmentalPotency
RELATION StemCell MAY_GENERATE ProgenitorCell
RELATION ProgenitorCell MAY_GENERATE DifferentiatedCell
RELATION StemCellNiche REGULATES StemCell
RELATION SignallingPathway REGULATES StemCellState
RELATION LineageTracing TRACKS StemCellDescendants
RELATION CellularReprogramming MAY_GENERATE InducedPluripotentStemCell
RELATION StemCell MAY_SUPPORT TissueMaintenance
RELATION StemCell MAY_SUPPORT Regeneration

SEMANTIC_EQUIVALENCE {
 "stem cell" ~= "self-renewing cell with developmental potency" WHEN functional_definition
 "iPSC" ~= "induced pluripotent stem cell"
 "HSC" ~= "hematopoietic stem cell"
 "stem cell niche" ~= "local stem-cell-regulating microenvironment"
 "self-renewal" ~= "division maintaining stem cell identity or pool"
 "potency" ~= "range of possible developmental cell fates" WHEN stem_cell_context
}

CONFIDENCE StemCellAssertion {
 INPUTS: [self_renewal_support, lineage_support, potency_support, functional_support, molecular_support, epigenetic_support, transplantation_support, clonal_support, source_independence, semantic_consistency]
 SCORE := weighted_sum(INPUTS)
 LEVEL :=
  IF SCORE >= 0.90 THEN "very_high"
  ELSE IF SCORE >= 0.75 THEN "high"
  ELSE IF SCORE >= 0.55 THEN "moderate"
  ELSE IF SCORE >= 0.35 THEN "low"
  ELSE "uncertain"
}

RULE StemCellIdentityInference {
 IF long_term_self_renewal
 AND appropriate_lineage_potential ARE_SUPPORTED
 THEN StemCellIdentity MAY_BE_SUPPORTED
 WITH context_specific_definition
}

RULE PotencyInference {
 IF single_cell_or_clonal_descendants generate_multiple_defined_lineages
 UNDER validated_conditions
 THEN DevelopmentalPotency MAY_BE_SUPPORTED
}

RULE NicheInference {
 IF niche_component_perturbation reproducibly_changes stem_cell_state
 THEN niche_regulatory_relationship MAY_BE_SUPPORTED
}

RULE ReprogrammingInference {
 IF somatic_cell transitions_to_pluripotent_molecular_and_functional_state
 THEN CellularReprogramming MAY_BE_SUPPORTED
}

RULE CausalityConstraint {
 IF stem_cell_marker correlates_with regenerative_or_developmental_outcome
 THEN DO_NOT_INFER causal_stem_cell_function
 WITHOUT lineage_functional_or_interventional_evidence
}

QUERY StemCellLookup(cell_identifier) {
 RETURN [identity, tissue, potency, self_renewal, niche, markers, signalling, metabolism, lineage_outputs, functional_assays, evidence, confidence]
}

QUERY StemCellNicheLookup(niche_identifier) {
 RETURN [tissue, stem_cell_population, neighbouring_cells, extracellular_matrix, soluble_signals, mechanical_context, metabolic_context, regulatory_effects, evidence, confidence]
}

QUERY StemCellLineageLookup(lineage_identifier) {
 RETURN [stem_cell, progenitors, branch_points, differentiated_descendants, potency_changes, developmental_time, lineage_tracing, functional_evidence, confidence]
}

UPDATE_MODEL {
 ON new_stem_cell_evidence:
  validate_provenance()
  identify_organism_tissue_and_cell_context()
  normalize_stem_progenitor_marker_and_lineage_identifiers()
  classify_potency_state()
  capture_niche_or_culture_context()
  capture_measurement_method_and_timepoint()
  map_self_renewal_and_division_modes()
  map_lineage_commitment_and_differentiation()
  map_signalling_metabolic_and_epigenetic_regulation()
  map_tissue_maintenance_regeneration_and_clonal_dynamics()
  compare_existing_stem_cell_models()
  preserve_conflicting_evidence()
  recalculate_confidence()
  regenerate_stem_cell_relationships()
  update_flow_hash()
}

AI_CONSUMPTION {
 MODE: FormalSemanticReasoning
 PARSE_AS: ExecutableFlowAlgebra
 PRIORITIES: [stem_cell_identity, self_renewal, developmental_potency, tissue_context, niche, lineage, differentiation, functional_evidence, evidence_provenance, confidence]
 REQUIREMENTS: [preserve_species_and_tissue_context, preserve_cell_state_and_potency, preserve_niche_or_culture_context, distinguish_proliferation_from_self_renewal, distinguish_stem_cell_from_progenitor_cell, distinguish_marker_expression_from_functional_identity, distinguish_pluripotency_markers_from_complete_reprogramming, distinguish_stem_cell_activation_from_complete_regeneration, distinguish_association_from_causation, preserve_uncertainty]
}

VALIDATE {
 REQUIRE StemCell
 REQUIRE SelfRenewal
 REQUIRE DevelopmentalPotency
 REQUIRE EmbryonicStemCell
 REQUIRE AdultStemCell
 REQUIRE InducedPluripotentStemCell
 REQUIRE StemCellNiche
 REQUIRE Quiescence
 REQUIRE StemCellDivision
 REQUIRE ProgenitorCell
 REQUIRE LineageCommitment
 REQUIRE Differentiation
 REQUIRE LineageTracing
 REQUIRE FunctionalStemCellEvidence
 REQUIRE Evidence
 REQUIRE CONFIDENCE
 REQUIRE SEMANTIC_EQUIVALENCE
 REQUIRE UPDATE_MODEL
 REQUIRE AI_CONSUMPTION

 ASSERT cell_proliferation != self_renewal
 ASSERT StemCell != ProgenitorCell
 ASSERT marker_expression != demonstrated_potency
 ASSERT pluripotency_marker_induction != complete_reprogramming
 ASSERT stem_cell_activation != complete_regeneration
 ASSERT correlation != causal_stem_cell_function
}

FLOW_HASH {
 ALGORITHM: SHA-256
 INPUT: canonicalize(entities, relations, processes, rules, semantic_equivalence, confidence_model, update_model, ai_consumption)
 PURPOSE: integrity_and_version_tracking
}

END flow "StemCellOntology"