Endothelial development terms need relocation

[gocentral]

Endothelial development (go:0003158) "Is a" epithelium development (go:0060429) and endothelial cell differentiation (go:0045446) "is a" epithelial cell differentiation (go:0030855)

These do not reflect the current consensus regarding endothelial development. Endothelial cells apparently derive from bone marrow cells, which are quite distinct/distant in origin from epithelial cells.

Endothelial cells line blood vessels, lymph vessels, and some other body cavities. Epithelial cells "face the outside world"...ie skin, lining of the gut, lining of the lung, etc.

Reported by: lowr

Original Ticket: geneontology/ontology-requests/8626

[gocentral]

moving to ontology content tracker

Original comment by: mah11

[gocentral]

• assigned_to: nobody --> ukemi

Original comment by: rebeccafoulger

[gocentral]

• labels: --> development

Original comment by: rebeccafoulger

[gocentral]

Hi Tim,

This is a very interesting observation and it is one that we thought about when we were considering the placement of this term. It touches on two points. First, it is true that endothelial cells derive from different origins than traditional epithelial cells. However, one of the first rules of describing development in GO that Tanya and I followed was not use developmental lineage as a criteria for development in GO. Consider epithelial cells in plants vs. animals for an obvious reason why this can't be done. A more subtle example with endotheia would be trying to do this with corneal endothelium (neural crest-derived) vs. blood vessel endothelium (BM-derived). Instead, we decided that the best place to describe 'develops_from' relationships would be in the gross anatomical and cell type ontologies. I have been in contact with Terry Meehan, the curator of the cell type ontology, and in the cell type ontology an endothelial cell is defined as a meso-epithelial cell. A meso-epithelial cell is an epithelial cell derived from mesoderm or mesenchyme. So, in the cell type ontology, they do reflect the lineage.

Second, when thinking about the characteristics of epithelia and endothelia, the only discriminating feature is the one you describe in this item, the inside versus outside. However, if we consider defining these structures morphologically, then they are in fact very similar. They are composed of 'sheets' of cells that arrange in 2-dimensional structure. There are many references in the literature that refer to endothelia as epithelia, in particular squamous epithelia. Lastly, when we think about the developmental/morphological processes that occur in epithelia and endothelia, they would both include epithelial/endothelial to mesenchymal transitions and the converse. These processes are very similar (PMID:17384082) and are currently the subject of lots of work. Scanning the literature over the last few years implies that people still lump these processes together and many people still consider endothelia to be squamous epithelia. For these reasons we are tempted to leave endothelium as an epithelium for now.

Of course since this was a difficult decision for us to begin with, we are open to further discussion. Do you have some references that would strongly argue for the separation?

David

Original comment by: ukemi

[gocentral]

Hi David-

After some further checking, I think it should stay "as is", even though it is confusing. There are too many conflicting usages of "epithelial cells" as well as "endothelial cells". Within the "blood vessel studies" community, the term "endothelial" seems to have a distinct meaning, but in the world at large, the definition becomes much fuzzier.

I'm sure the relationship will cause other users some confusion, but hopefully, it will be minor and temporary.

I can agree with your definition of "epithelium", but your definition of endothelium as "An epithelium that lines an anatomical structure" is not specific enough. For instance, cells that line the lungs, bladder, (and renal tubules), and intestine are always referred to as epithelium, not endothelium. I guess I am more comfortable with the concept of endothelium as a sister term to epithelium, not a daughter term. Even though I now understand your reasons for putting it there!

GO has many more granular references to endothelium that may make my objections unimportant. If someone is interested in "vessel endothelium", there are plenty of paths to that term.

So like I said at the top, maybe it should just stay as is!

Tim

Original comment by: lowr

[gocentral]

Hi Tum,

>but your definition of endothelium as "An epithelium that lines an anatomical structure" is not >specific enough. For instance, cells that line the lungs, bladder, (and renal tubules), and intestine are >always referred to as epithelium, not endothelium.

Yup! You are correct. Any suggestions?

David

Original comment by: ukemi

[gocentral]

Hi David-

I spoke with a couple other people about the issue, and those who expressed an opinion preferred that endothelial cells be given "sister status" relative to epithelial cells, since they have distinct origins. The parent-child relationship is valid from a morphological/ conceptual standpoint, but it can also be misconstrued to be a developmental relationship, which is not correct.

Regarding the definition, I would suggest: "Endothelium refers to the layer of cells lining blood vessels, lymphatics, the heart, and serous cavities, and is derived from bone marrow or mesoderm. Corneal endothelium is a special case, derived from neural crest cells." I avoided using the word "epithelium", although several definitions I found do not. What is important, I think, is that "endothelium" refers only to cells in the specified locations, where their functions are unique to that location. The same distinction could be made for "epithelial cells" at their various locations. In publications, the identification is usually explicit, as in "alveolar epithelium".

Tim

Original comment by: lowr

[gocentral]

OK. I think I have finally sorted these terms correctly. I used the definition provided below.

David

Original comment by: ukemi

[gocentral]

• status: open --> closed-fixed

Original comment by: ukemi

[gocentral]

The change wasn't made consistently:

http://cvsweb.geneontology.org/cgi-bin/cvsweb.cgi/go/ontology/editors/gene\_ontology\_write.obo.diff?r1=1.2587;r2=1.2588;f=h

We now have two implicit endothelium sub-ontologies in GO, one in which it's classified as epithelium, the other not.

I'm not so keen on GO making this decision unilaterally, independently of the cell ontology and all the anatomy ontologies. The primary definition and classification should live there. Note that the GO should derive its hierarchy and definitions automatically from these sources.

I am happy with whatever the experts decide, but it should be fixed at source, and percolated from there.

Tim, you said:

"The parent-child relationship is valid from a morphological/ conceptual standpoint, but it can also be misconstrued to be a developmental relationship, which is not correct. "

This would be a mis-reading of the isa relationship - there should be no implication of a developmental relationship.

One option would be to subclass epithelial cell into "true" epithelial cell and endothelia

Original comment by: cmungall

[gocentral]

• status: closed-fixed --> open-fixed

Original comment by: cmungall

[gocentral]

Hi Chris,

I thought that I had caught all the endothelia and reclassified them as sibs, but maybe not. It is difficult to make these changes consistently due to the size of the ontology. I am happy to revert back if that is what the expert anatomists/cell biologists decide.

David

Original comment by: ukemi

[ukemi]

Closing this issue as out of date because as Chris points out above, these terms now live as cross-products with the corresponding terms from the external ontologies. If the placement is incorrect,, it will have to be changed by the experts that curate those ontologies. GO is consistent with their representation.