DifferentiationPub Date : 2023-09-01DOI: 10.1016/j.diff.2023.08.002
Er-li Wu , Ming Cheng , Xin-jing Zhang , Tian-gang Wu , Lei Zhang
{"title":"The role of non-coding RNAs in diabetes-induced osteoporosis","authors":"Er-li Wu , Ming Cheng , Xin-jing Zhang , Tian-gang Wu , Lei Zhang","doi":"10.1016/j.diff.2023.08.002","DOIUrl":"10.1016/j.diff.2023.08.002","url":null,"abstract":"<div><p>Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP. Recently, non-coding RNAs (ncRNAs) have received more attention due to their significant role in cellular functions and bone formation. It is worth noting that ncRNAs have also been demonstrated to participate in the progression of DOP. Meanwhile, nano-delivery systems are considered a promising strategy to treat DOP because of their cellular targeting, sustained release, and controlled release characteristics. Additionally, the utilization of novel technologies such as the CRISPR system has expanded the scope of available options for treating DOP. Hence, this paper explores the functions and regulatory mechanisms of ncRNAs in DOP and highlights the advantages of employing nanoparticle-based drug delivery techniques to treat DOP. Finally, this paper also explores the potential of ncRNAs as diagnostic DOP biomarkers.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"133 ","pages":"Pages 98-108"},"PeriodicalIF":2.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-08-23DOI: 10.1016/j.diff.2023.08.003
Carmen Grimaldos Rodriguez , Ella F. Rimmer , Benjamin Colleypriest , David Tosh , Jonathan M.W. Slack , Ute Jungwirth
{"title":"Ectopic expression of HNF4α in Het1A cells induces an invasive phenotype","authors":"Carmen Grimaldos Rodriguez , Ella F. Rimmer , Benjamin Colleypriest , David Tosh , Jonathan M.W. Slack , Ute Jungwirth","doi":"10.1016/j.diff.2023.08.003","DOIUrl":"10.1016/j.diff.2023.08.003","url":null,"abstract":"<div><p>Barrett's oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an <em>in vitro</em> system for examining the competitive behaviour of two epithelia. We find that when an oesophageal epithelium model (Het1A cells) is confronted by an intestinal epithelium model (Caco-2 cells), the intestinal cells expand into the oesophageal domain. In this case the boundary involves overgrowth by the Caco-2 cells and the formation of isolated colonies. Two key transcription factors, normally involved in intestinal development, HNF4α and CDX2, are both expressed in BO. We examined the competitive ability of Het1A cells stably expressing HNF4α or CDX2 and placed in confrontation with unmodified Het1A cells. The key result is that stable expression of HNF4α, but not CDX2, increased the ability of the cells to migrate and push into the unmodified Het1A domain. In this situation the boundary between the cell types is a sharp one, as is normally seen in BO. The experiments were conducted using a variety of extracellular substrates, which all tended to increase the cell migration compared to uncoated plastic. These data provide evidence that HNF4α expression could have a potential role in the competitive spread of BO into the oesophagus as HNF4α increases the ability of cells to invade into the adjacent stratified squamous epithelium, thus enabling a single mutant cell eventually to generate a macroscopic patch of metaplasia.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"134 ","pages":"Pages 1-10"},"PeriodicalIF":2.9,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10204864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.02.002
Shivalingappa K. Swamynathan , Sudha Swamynathan
{"title":"Corneal epithelial development and homeostasis","authors":"Shivalingappa K. Swamynathan , Sudha Swamynathan","doi":"10.1016/j.diff.2023.02.002","DOIUrl":"10.1016/j.diff.2023.02.002","url":null,"abstract":"<div><p>The corneal epithelium (CE), the most anterior cellular structure of the eye, is a self-renewing stratified squamous tissue that protects the rest of the eye from external elements. Each cell in this exquisite three-dimensional structure needs to have proper polarity and positional awareness for the CE to serve as a transparent, refractive, and protective tissue. Recent studies have begun to elucidate the molecular and cellular events involved in the embryonic development, post-natal maturation, and homeostasis of the CE, and how they are regulated by a well-coordinated network of transcription factors. This review summarizes the status of related knowledge and aims to provide insight into the pathophysiology of disorders caused by disruption of CE development, and/or homeostasis.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 4-14"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10660906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.01.002
Tyler Schwend
{"title":"Wiring the ocular surface: A focus on the comparative anatomy and molecular regulation of sensory innervation of the cornea","authors":"Tyler Schwend","doi":"10.1016/j.diff.2023.01.002","DOIUrl":"10.1016/j.diff.2023.01.002","url":null,"abstract":"<div><p>The cornea is richly innervated with sensory nerves that function to detect and clear harmful debris from the surface of the eye, promote growth and survival of the corneal epithelium and hasten wound healing following ocular disease or trauma. Given their importance to eye health, the neuroanatomy of the cornea has for many years been a source of intense investigation. Resultantly, complete nerve architecture maps exist for adult human and many animal models and these maps reveal few major differences across species. Interestingly, recent work has revealed considerable variation across species in how sensory nerves are acquired during developmental innervation of the cornea. Highlighting such species-distinct key differences, but also similarities, this review provides a full, comparative anatomy analysis of sensory innervation of the cornea for all species studied to date. Further, this article comprehensively describes the molecules that have been shown to guide and direct nerves toward, into and through developing corneal tissue as the final architectural pattern of the cornea’s neuroanatomy is established. Such knowledge is useful for researchers and clinicians seeking to better understand the anatomical and molecular basis of corneal nerve pathologies and to hasten neuro-regeneration following infection, trauma or surgery that damage the ocular surface and its corneal nerves.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 24-40"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.04.005
Sudhir Verma , Isabel Y. Moreno , Morgan E. Trapp , Luis Ramirez , Tarsis F. Gesteira , Vivien J. Coulson-Thomas
{"title":"Meibomian gland development: Where, when and how?","authors":"Sudhir Verma , Isabel Y. Moreno , Morgan E. Trapp , Luis Ramirez , Tarsis F. Gesteira , Vivien J. Coulson-Thomas","doi":"10.1016/j.diff.2023.04.005","DOIUrl":"10.1016/j.diff.2023.04.005","url":null,"abstract":"<div><p>The Meibomian gland (MG) is an indispensable adnexal structure of eye that produces meibum, an important defensive component for maintaining ocular homeostasis. Normal development and maintenance of the MGs is required for ocular health since atrophic MGs and disturbances in composition and/or secretion of meibum result in major ocular pathologies, collectively termed as Meibomian gland dysfunction (MGD). Currently available therapies for MGD merely provide symptomatic relief and do not treat the underlying deficiency of the MGs. Hence, a thorough understanding of the timeline of MG development, maturation and aging is required for regenerative purposes along with signaling molecules & pathways controlling proper differentiation of MG lineage in mammalian eye. Understanding the factors that contribute to the development of MGs, developmental abnormalities of MGs, and changes in the quality & quantity of meibum with developing phases of MGs are essential for developing potential treatments for MGD. In this review, we compiled a timeline of events and the factors involved in the structural and functional development of MGs and the associated developmental defects of MGs during development, maturation and aging.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 41-50"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.04.002
Wenjie Yin , Xiying Mao , Miao Xu, Mingkang Chen, Mengting Xue, Na Su, Songtao Yuan, Qinghuai Liu
{"title":"Epigenetic regulation in the commitment of progenitor cells during retinal development and regeneration","authors":"Wenjie Yin , Xiying Mao , Miao Xu, Mingkang Chen, Mengting Xue, Na Su, Songtao Yuan, Qinghuai Liu","doi":"10.1016/j.diff.2023.04.002","DOIUrl":"10.1016/j.diff.2023.04.002","url":null,"abstract":"<div><p>Retinal development is initiated by multipotent retinal progenitor cells, which undergo several rounds of cell divisions and subsequently terminal differentiation. Retinal regeneration is usually considered as the recapitulation of retinal development, which share common mechanisms underlying the cell cycle re-entry of adult retinal stem cells and the differentiation of retinal neurons. However, how proliferative retinal progenitor cells perform a precise transition to postmitotic retinal cell types during the process of development and regeneration remains elusive. It is proposed that both the intrinsic and extrinsic programming are involved in the transcriptional regulation of the spatio-temporal fate commitment. Epigenetic modifications and the regulatory mechanisms at both DNA and chromatin levels are also postulated to play an important role in the timing of differentiation of specific retinal cells. In the present review, we have summarized recent knowledge of epigenetic regulation that underlies the commitment of retinal progenitor cells in the settings of retinal development and regeneration.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 51-58"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.06.004
Anna La Torre, Peter Lwigale
{"title":"Ocular development: A view from the front to the back of the eye","authors":"Anna La Torre, Peter Lwigale","doi":"10.1016/j.diff.2023.06.004","DOIUrl":"10.1016/j.diff.2023.06.004","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 1-3"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-07-01DOI: 10.1016/j.diff.2023.02.003
Georgios Tsissios , Gabriella Theodoroudis-Rapp , Weihao Chen , Anthony Sallese , Byran Smucker , Lake Ernst , Junfan Chen , Yiqi Xu , Sophia Ratvasky , Hui Wang , Katia Del Rio-Tsonis
{"title":"Characterizing the lens regeneration process in Pleurodeles waltl","authors":"Georgios Tsissios , Gabriella Theodoroudis-Rapp , Weihao Chen , Anthony Sallese , Byran Smucker , Lake Ernst , Junfan Chen , Yiqi Xu , Sophia Ratvasky , Hui Wang , Katia Del Rio-Tsonis","doi":"10.1016/j.diff.2023.02.003","DOIUrl":"10.1016/j.diff.2023.02.003","url":null,"abstract":"<div><h3>Background</h3><p>Aging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime.</p></div><div><h3>Results</h3><p>Here, we used Spectral-Domain Optical Coherence Tomography (SD-OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related change in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms.</p></div><div><h3>Conclusions</h3><p>Collectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes associated with aging alter the kinetics of this process. By understanding how these changes affect lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"132 ","pages":"Pages 15-23"},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10573632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-05-01DOI: 10.1016/j.diff.2023.03.002
Michał M. Hryciuk , Filip Schröter , Luise Hennicke , Beate C. Braun
{"title":"Spheroid formation and luteinization of granulosa cells of felids in a long-term 3D culture","authors":"Michał M. Hryciuk , Filip Schröter , Luise Hennicke , Beate C. Braun","doi":"10.1016/j.diff.2023.03.002","DOIUrl":"10.1016/j.diff.2023.03.002","url":null,"abstract":"<div><p>In the present study, granulosa cells (GCs) from domestic cats and Persian leopard were cultured and characterized from selected days. The culture period was divided into two phases: maintenance, which lasted for 7 days, and luteinization, which followed for up to 11 days. Luteinization was performed on ultra-low attachment plates, supporting the formation of spheroids in a medium supplemented with insulin, forskolin, and luteinizing hormone (LH). GCs of domestic cat produced estradiol (E2) and progesterone (P4) during the maintenance phase. The gene expressions of some proteins involved in steroidogenesis were stable (<em>STAR</em>, <em>HSD3B1</em>) or decreased over time (<em>CYP11A1</em>, <em>HSD17B1</em>, <em>CYP17A1</em>, and <em>CYP19A1</em>), which was similar to the expressions of gonatropin receptors (<em>LHCGR</em> and <em>FSHR</em>). During the luteinization phase, P4 concentration significantly increased (<em>P</em> < 0.05), and E2, in contrast to the proliferation phase, was below detection range. The expression of genes of proteins involved in steroidogenesis (<em>STAR</em>, <em>CYP11A1</em>, <em>HSD3B1</em>, <em>HSD17B1</em>, <em>CYP17A1</em>, and <em>CYP19A1</em>) and of gonadotropin receptors (<em>LHCGR</em> and <em>FSHR</em>) significantly increased during the luteinization period, but some expressions exhibited a decrease at the end of the phase (<em>LHCGR</em>, <em>FSHR</em>, <em>HSD17B1</em>, <em>CYP19A1</em>). The morphology of the luteinized GCs of domestic cat resembled large luteal cells and had numerous vacuole-like structures. Also, the GCs of Persian leopard underwent luteinization, shown by increasing P4 production and <em>HSD3B1</em> expression. This study confirms that GCs from felids can be luteinized in a 3D spheroid system which can be a basis for further studies on luteal cell function of felids. Additionally, we could show that the domestic cat can serve as a model species for establishing cell culture methods which can be transferred to other felids.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"131 ","pages":"Pages 38-48"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9681931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DifferentiationPub Date : 2023-05-01DOI: 10.1016/j.diff.2023.04.001
Sierra S. Marable, Marianne E. Bronner
{"title":"Reprogramming of trunk neural crest to a cranial crest-like identity alters their transcriptome and developmental potential","authors":"Sierra S. Marable, Marianne E. Bronner","doi":"10.1016/j.diff.2023.04.001","DOIUrl":"10.1016/j.diff.2023.04.001","url":null,"abstract":"<div><p>Neural crest cells along the body axis of avian embryos differ in their developmental potential, such that the cranial neural crest forms cartilage and bone whereas the trunk neural crest is unable to do so. Previous studies have identified a cranial crest-specific subcircuit that can imbue the trunk neural crest with the ability to form cartilage after grafting to the head. Here, we examine transcriptional and cell fate changes that accompany this reprogramming. First, we examined whether reprogrammed trunk neural crest maintain the ability to form cartilage in their endogenous environment in the absence of cues from the head. The results show that some reprogrammed cells contribute to normal trunk neural crest derivatives, whereas others migrate ectopically to the forming vertebrae and express cartilage markers, thus mimicking heterotypically transplanted cranial crest cells. We find that reprogrammed trunk neural crest upregulated more than 3000 genes in common with cranial neural crest, including numerous transcriptional regulators. In contrast, many trunk neural crest genes are downregulated. Together, our findings show that reprogramming trunk neural crest with cranial crest subcircuit genes alters their gene regulatory program and developmental potential to be more cranial crest-like.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"131 ","pages":"Pages 27-37"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}