Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes

<p><strong>Background:</strong><br /> Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing with...

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Hoofdauteurs: Paterson, YZ, Cribbs, A, Espenel, M, Smith, EJ, Henson, FMD, Guest, DJ
Formaat: Journal article
Taal:English
Gepubliceerd in: BioMed Central 2020
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author Paterson, YZ
Cribbs, A
Espenel, M
Smith, EJ
Henson, FMD
Guest, DJ
author_facet Paterson, YZ
Cribbs, A
Espenel, M
Smith, EJ
Henson, FMD
Guest, DJ
author_sort Paterson, YZ
collection OXFORD
description <p><strong>Background:</strong><br /> Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic.</p><br /> <p><strong>Methods:</strong><br /> Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing.</p><br /> <p><strong>Results:</strong><br /> No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes’ transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells’ gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed.</p><br /> <p><strong>Conclusion:</strong><br /> The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages.</p>
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spelling oxford-uuid:e6f6e44d-a07b-45d1-9858-f07c4c2c2a982022-03-27T10:34:51ZGenome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e6f6e44d-a07b-45d1-9858-f07c4c2c2a98EnglishSymplectic ElementsBioMed Central2020Paterson, YZCribbs, AEspenel, MSmith, EJHenson, FMDGuest, DJ<p><strong>Background:</strong><br /> Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic.</p><br /> <p><strong>Methods:</strong><br /> Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing.</p><br /> <p><strong>Results:</strong><br /> No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes’ transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells’ gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed.</p><br /> <p><strong>Conclusion:</strong><br /> The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages.</p>
spellingShingle Paterson, YZ
Cribbs, A
Espenel, M
Smith, EJ
Henson, FMD
Guest, DJ
Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title_full Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title_fullStr Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title_full_unstemmed Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title_short Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes
title_sort genome wide transcriptome analysis reveals equine embryonic stem cell derived tenocytes resemble fetal not adult tenocytes
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AT espenelm genomewidetranscriptomeanalysisrevealsequineembryonicstemcellderivedtenocytesresemblefetalnotadulttenocytes
AT smithej genomewidetranscriptomeanalysisrevealsequineembryonicstemcellderivedtenocytesresemblefetalnotadulttenocytes
AT hensonfmd genomewidetranscriptomeanalysisrevealsequineembryonicstemcellderivedtenocytesresemblefetalnotadulttenocytes
AT guestdj genomewidetranscriptomeanalysisrevealsequineembryonicstemcellderivedtenocytesresemblefetalnotadulttenocytes