If knocking out a transcription factor in the liver prevents hepatocytes from differentiating, would it make sense to search for the proteins that are targets of the transcription factor and known to be involved in differentiation in other tissues/cells?
Hai Ms.Arora, if the protein you are interested/picked, plays a major role in differentiation of a cell type, I think the chance is less for it to play such a crucial role in another tissue. But the proteins that are targets of pro- anti- differentiation factors (it can be TFs also) is likely to play role in different tissues. This in just my opinion based on my experience in adipocyte differentiation studies.
Dear Gunisha, every tissue has a specific kind of protein expressed in it. And I think this is the key which each tissue has its specific function.
Example exist on both sides- sometimes transcription factors have similar sets of downstream targets in different tissues, while in other cases there is little overlap (for example PPARg targets in adipocytes vs. macrophages). The fact that your transcription factor is expressed in liver probably doesn't tip the scales towards one scenario vs. the other.
Moreover, transcription factors often influence differentiation by regulating a whole network of genes, rather than just one or two essential players. As a result, you can't necessarily explain the role of a specific transcription factor in differentiation to be explained by the expression of just a few response genes.
Perhaps if you provide a bit more context or detail to your question, a more specific answer or research strategy can be provided.
I am trying to analyze this based on the fact that this TF has a no. of targets, and is functional not only in liver but also in chondrocytes, protrate etc.. But, within this panel of target genes there are those that are involved in differentiation in other tissues/cells under the influence of this TF. So I should be able to identify those proteins involved in differentiation of hepatocytes using the common pool of target genes involved in differentiation.
I hope this is not too confusing!
How do you plan on using this information? While I agree that if a particular gene is involved in differentiation in multiple tissues, it is more likely than not to play a role in your tissue of interest (liver), I'm not sure this will help you understand how it contributes to hepatocyte differentiation, per se. Differentiation involves both general factors and tissue-specific factors, both of which are required to complete the process of cell fate specification.
Whether identifying a factor that plays a generalized or permissive function in differentiation is useful to your research program depends a lot on what you are trying to accomplish.
How does one go about looking for tissue specific differentiation factors in an oval cell that is unable to terminally differentiate...?
Can you isolate these cells or can the liver oval cells only be identified in vivo? This has some impact on how you would proceed.
I suggest you search archived databases for the target genes. Then, you can look in the archived databases for signature gene expression profiles to determine tissues or cells that have the signature transcriptome suggesting the involvement of that particular transcription factor.
You question may be viewed a little too broad. The transcription factor may have a similar role in different tissues for cells that have the same or similar biological features. Example, macrophages in bone marrow, liver, lungs may have a similar response pattern to a particular transcription factor. Hence, it will be also important for you to determine if the effects you observed at the tissue level represent direct effects at the level of hepatocytes or indirect effects mediated by non-hepatocyte cell populations in the liver that support the differentiation.
Best of luck in your research
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