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Event: 1560

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Cell differentiation, altered

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
cell differentiation	cell	abnormal

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
HDAC inhibition leads to neural tube defects	KeyEvent	Marvin Martens (send email)	Under Development: Contributions and Comments Welcome

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Mus musculus	Mus musculus	Moderate	NCBI
Homo sapiens	Homo sapiens	High	NCBI
Animals	Metazoa	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Pregnancy	Moderate
Embryo	High
Fetal	High
All life stages

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Cell differentiation is the process by which an undifferentiated cell develops into a specialized cell type with a distinct structure and function. Differentiation is a critical part of development because it results in cells with specialized characteristics like muscle, organ, neuron, and blood cells.

The stages of differentiation include a stem cell stage, a progenitor cell stage (also known as the transit-amplifying cell stage), and a terminally differentiated cell stage. In the stem cell stage, asymmetric stem cell division, with few exceptions, typically yields one daughter cell that rejoins the stem cell population and a second daughter cell that becomes targeted for differentiation and thus becomes a progenitor cell. In the progenitor cell stage, cell division produces additional daughter cells that are partly differentiated, becoming increasingly specialized with each round of cell division. Progenitor cells are restricted to a limited number of divisions before committing to a particular cell type. Terminal differentiation, in which cells become defined by specific properties, marks the end of cell division. (https://www.britannica.com/science/cell-differentiation)

Proper differentiation during embryonic development is regulated by the expression of genes at the right time and space. If key regulator genes are not expressed or wrongly expressed this leads to a different cell type.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Differentiation can be measured e.g. by in vitro hESC or iPSC based differentiation systems. Pre-requisite for this is a well characterized and homogenous cell population. Then it can be measured by the analysis of altered genes by gene set enrichment analysis (GEA) comparing control with potentially disturbed differentiation.

In the context of embryonic brain development, immunofluorescence on brain sections can be used with antibodies against neuronal differentiation markers such Tuj1, NeuN and betaIII-tubulin.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Cell differentiation happens throughout all lifestages but is most critical and widespread during embryonic and fetal development. It is the central process by which cells are specialized into thier eventual forms and functions.

In postnatal life and adulthood differentiation continues but in a more specific context, i.e., tissue maintenance, repair, and response to injury, and at a much lower scale.

Differentiation is a fundamental characteristic of essentially all multicellular organisms.

References

List of the literature that was cited for this KE description. More help

https://www.britannica.com/science/cell-differentiation