Differentiation最新文献_第6页

Letter to the Editor regarding: “Fgf8 promotes survival of nephron progenitors by regulating BAX/BAK mediated apoptosis” by Matthew J. Anderson, et al 关于Matthew J. Anderson等人的“Fgf8通过调节BAX/BAK介导的细胞凋亡促进肾元祖细胞的存活”的致编辑信

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-04-26 DOI: 10.1016/j.diff.2025.100864

Jian Wu , Wenya Gao , Ruili Li , Mingfei Yang

引用次数: 0

New genetic tools to define the pathophysiology of inborn errors of cobalamin metabolism impacting mammalian development 新的遗传工具来定义影响哺乳动物发育的先天性钴胺素代谢错误的病理生理学

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-05-19 DOI: 10.1016/j.diff.2025.100868

Tiffany Chern , Xuefei Tong , William G. Bauer , David J. Quispe-Parra , Xia Gao , Kamryn N. Gerner-Mauro , Ross A. Poché

{"title":"New genetic tools to define the pathophysiology of inborn errors of cobalamin metabolism impacting mammalian development","authors":"Tiffany Chern , Xuefei Tong , William G. Bauer , David J. Quispe-Parra , Xia Gao , Kamryn N. Gerner-Mauro , Ross A. Poché","doi":"10.1016/j.diff.2025.100868","DOIUrl":"10.1016/j.diff.2025.100868","url":null,"abstract":"<div><div>The congenital, autosomal recessive disorder combined methylmalonic acidemia and homocystinuria – <em>cblC</em> type, is the most common inborn error of cobalamin (vitamin B<sub>12</sub>) metabolism. In its early onset form, <em>cblC</em> profoundly impacts fetal development of the central nervous system, hematopoietic system, and other tissues. Previously, mutations in the <em>MMACHC</em> gene, which encodes a protein required for the intracellular trafficking and enzymatic processing of free cobalamin into active coenzyme forms, were found to cause <em>cblC</em>. These coenzymes are required in two metabolic pathways which produce either succinyl-CoA in the mitochondria or methionine in the cytosol. However, due to a lack of sufficient animal models, the exact pathophysiology of <em>cblC</em> remains unknown. Moreover, there is evidence to suggest that MMACHC may have roles outside of cobalamin metabolism and that cobalamin itself may be required for additional, unknown metabolic pathways. Here, we report the generation and characterization of three new mouse lines aimed at further defining the role of MMACHC and cobalamin in mammalian development. CRISPR/Cas9 genome editing was used to develop an HA-tagged version of <em>Mmachc</em>, which will aid in affinity purification and spatiotemporal localization of the MMACHC protein. To clarify which metabolic perturbations downstream of <em>Mmachc</em> loss give rise to tissue-specific developmental defects, we also created floxed alleles for both methionine synthase <em>(Mtr)</em> and methylmalonyl-CoA mutase <em>(Mmut)</em>, which are the only known cobalamin dependent enzymes in mammals. In total, these new mouse models significantly expand upon the repertoire of genetic reagents to clarify the pathophysiology of <em>cblC</em> as well as define both the canonical and hypothesized noncanonical roles of MMACHC in mammalian development.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100868"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116295","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}

引用次数: 0

Fibroblast growth factor 22 成纤维细胞生长因子22

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1016/j.diff.2025.100860

Rise Furuta, Ayumi Miyake

{"title":"Fibroblast growth factor 22","authors":"Rise Furuta, Ayumi Miyake","doi":"10.1016/j.diff.2025.100860","DOIUrl":"10.1016/j.diff.2025.100860","url":null,"abstract":"<div><div>Fibroblast growth factor 22 (FGF22) is a member of the FGF7 subfamily that functions as a paracrine factor and was identified in the human placenta in 2001. The <em>FGF22</em> gene is located on human chromosome 19p13.3, mouse chromosome 10, and zebrafish chromosome 22 and is closely linked to the <em>BSG, HCN2</em>, and <em>POLRMT</em> genes. The gene is composed of three exons, which are common in humans, mice, and zebrafish. However, in humans and mice, FGF22 is produced as two isoforms by alternative splicing, whereas no isoforms have been reported in zebrafish. In humans, <em>FGF22</em> is expressed in the skin, brain, and ovaries, whereas in mice, it is expressed in the skin, brain, retina, spinal cord, and cochlea. Various abnormalities have been reported in these regions in <em>Fgf22</em> mutant mice. In zebrafish, <em>fgf22</em> is expressed in the forebrain, midbrain, and otic vesicles during embryogenesis, and an analysis of knockdown zebrafish models revealed an important role for <em>fgf22</em> in the process of brain formation. As expected from the results of these functional analyses, FGF22 is also associated with human diseases such as depression, spinal cord injury, hearing loss, and cancer.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100860"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697193","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}

引用次数: 0

FGFR3 signaling is essential for gastric cancer cell triggering the transition of BM-MSCs into tumor-associated MSCs FGFR3信号对于胃癌细胞触发BM-MSCs向肿瘤相关MSCs的转变至关重要

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI: 10.1016/j.diff.2025.100859

Xiang Wang , Xiaoli Cao , Baocheng Zhou , Jingyu Mei , Yuanyuan Li , Xinlan Zhao , Wei Zhu , Feng Huang , Li Sun , Mei Wang

{"title":"FGFR3 signaling is essential for gastric cancer cell triggering the transition of BM-MSCs into tumor-associated MSCs","authors":"Xiang Wang , Xiaoli Cao , Baocheng Zhou , Jingyu Mei , Yuanyuan Li , Xinlan Zhao , Wei Zhu , Feng Huang , Li Sun , Mei Wang","doi":"10.1016/j.diff.2025.100859","DOIUrl":"10.1016/j.diff.2025.100859","url":null,"abstract":"<div><div>Bone marrow-derived mesenchymal stem cells (BM-MSCs) tend to migrate towards tumor sites and interact with tumor cells, thus incorporating into tumor microenvironment by transition into various stromal cells, particularly tumor-associated MSCs. However, the mechanisms involved in this process is still not clarified. Herein, we focused on miR-99a-5p and confirmed its reduction in gastric cancer-associated MSCs (GC-MSCs) compared to BM-MSCs. Under-expression of miR-99a-5p stimulated BM-MSCs transition into GC-MSCs-like cells, while overexpression of this miRNA abrogated tumor-promoting roles of GC-MSCs. miR-99a-5p not only targeted modulation of fibroblast growth factor receptor (FGFR3) but also negatively affected its phosphorylated levels. Suppression of FGFR3 signaling by AZD4547 or siRNA against FGFR3 notably blocked the miR-99a-5p inhibitor-induced BM-MSCs transition and the oncogenic roles of GC-MSCs. However, miR-99a-5p overexpression did not diminish the ability of gastric cancer cells to educate BM-MSCs. The levels of phosphorylated FGFR3, but not total FGFR3, was increased in BM-MSCs educated by gastric cancer cells. AZD4547 significantly suppressed the education capacity of gastric cancer cells on BM-MSCs. Taken together, although manipulating miR-99a-5p to mimic its levels in GC-MSCs promotes the transition of BM-MSCs into GC-MSCs-like cells, FGFR3 signaling, rather than miR-99a-5p, is unexpectedly essential for the education of BM-MSCs by gastric cancer cells. This discovery provides a novel mechanism underlying the transition of BM-MSCs into tumor-associated MSCs and identifies potential therapeutic targets for gastric cancer.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100859"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643087","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}

引用次数: 0

NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos 非甾体抗炎药介导的环加氧酶抑制破坏美西螈胚胎外胚层衍生物的形成

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI: 10.1016/j.diff.2025.100856

Emma J. Marshall , Raneesh Ramarapu , Tess A. Leathers , Nikolas Morrison-Welch , Kathryn Sandberg , Maxim Kawashima , Crystal D. Rogers

{"title":"NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos","authors":"Emma J. Marshall , Raneesh Ramarapu , Tess A. Leathers , Nikolas Morrison-Welch , Kathryn Sandberg , Maxim Kawashima , Crystal D. Rogers","doi":"10.1016/j.diff.2025.100856","DOIUrl":"10.1016/j.diff.2025.100856","url":null,"abstract":"<div><div>Embryonic exposures to non-steroidal anti-inflammatory drugs (NSAIDs) have been linked to preterm birth, neural tube closure defects, abnormal enteric innervation, and craniofacial malformations, potentially due to disrupted neural tube or neural crest (NC) cell development. Naproxen (NPX), a common non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation, exerts its effects through non-selective cyclooxygenase (COX) inhibition. Our lab has identified that the cyclooxygenase (COX-1 and COX-2) isoenzymes are expressed during the early stages of vertebrate embryonic development, and that global inhibition of COX-1 and COX-2 function disrupts NC cell migration and differentiation in <em>Ambystoma mexicanum</em> (axolotl) embryos. NC cells differentiate into various adult tissues including craniofacial cartilage, bone, and neurons in the peripheral and enteric nervous systems. To investigate the specific phenotypic and molecular effects of NPX exposure on NC development and differentiation, and to identify molecular links between COX inhibition and NC derivative anomalies, we exposed late neurula and early tailbud stage axolotl embryos to various concentrations of NPX and performed immunohistochemistry (IHC) for markers of migratory and differentiating NC cells. Our results reveal that NPX exposure impairs the migration of SOX9+ NC cells, leading to abnormal development of craniofacial cartilage structures, including Meckel’s cartilage in the jaw. NPX exposure also alters the expression of markers associated with peripheral and central nervous system (PNS and CNS) development, suggesting concurrent neurodevelopmental changes.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100856"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715000","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}

引用次数: 0

The mechanism of EGF in promoting skeletal muscle post-injury regeneration 表皮生长因子促进骨骼肌损伤后再生的机制

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1016/j.diff.2025.100862

Huaixin Teng , Yongze Liu , Ruotong Hao , Lu Zhang , Xiaoyu Zhang , Shufeng Li , Shuang Li , Huili Tong

引用次数: 0

Chondrocalcin: Insights into its regulation and multi-function in cartilage and bone 软骨钙素：其在软骨和骨中的调节和多功能的见解

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1016/j.diff.2025.100861

Wensha Zhu , Zilong Zhao , Weigang Yuwen , Linlin Qu , Zhiguang Duan , Chenhui Zhu , Daidi Fan

引用次数: 0

RANKL promotes MT2 degradation and ROS production in osteoclast precursors through Beclin1-dependent autophagy RANKL通过beclin1依赖性自噬促进破骨细胞前体MT2降解和ROS产生

IF 2.2 3区生物学

Differentiation Pub Date : 2025-05-01 Epub Date: 2025-04-19 DOI: 10.1016/j.diff.2025.100863

Dianshan Ke , Tingwei Gao , Hanhao Dai , Jie Xu, Tie Ke

{"title":"RANKL promotes MT2 degradation and ROS production in osteoclast precursors through Beclin1-dependent autophagy","authors":"Dianshan Ke , Tingwei Gao , Hanhao Dai , Jie Xu, Tie Ke","doi":"10.1016/j.diff.2025.100863","DOIUrl":"10.1016/j.diff.2025.100863","url":null,"abstract":"<div><div>ROS produced under oxidative stress are crucial for osteoclast differentiation. Metallothionein (MT) is a ROS-scavenging molecule. As a member of MT family, MT2 can clear ROS in osteoclast precursors (OCPs) and contributes to osteoclast differentiation. RANKL can promote OCP autophagy. Given the molecular-degrading effect of autophagy, the relationship between RANKL-dependent autophagy, MT2 and ROS during osteoclast differentiation is worth exploring. We depended <em>in vitro</em> RANKL administration and RANKL-overexpressing (Tg-RANKL) mice to observe the effects of RANKL on ROS production, MT2 protein expression, Beclin1 expression and autophagic activity in OCPs. Spautin1 was used to investigate the relationship between Beclin1-dependent autophagy and RANKL-regulated MT2 expression. Osteoclast-targeting MT2-cDNA-AAVs were applied to assess the therapeutic effect of MT2 on Tg-RANKL-related bone loss. The results showed that RANKL promoted ROS production but reduced MT2 protein expression in OCPs. RANKL also enhanced Beclin1 expression and LC3-puncta abundance. Decreased Beclin1 expression with spautin1 blocked RANKL-increased ROS production and osteoclast differentiation and recovered RANKL-decreased MT2 expression. MT2 selective overexpression with CD11b-promoter-MT2-cDNA-AAVs attenuated ROS production and osteoclastogenesis in Tg-RANKL mice and improved bone loss. Overall, RANKL can reduce MT2 protein expression through Beclin1-dependent autophagy, thereby promoting ROS production and osteoclast differentiation; this suggests that MT2-overexpressing small molecule drugs have the potential to treat RANKL-related bone loss.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100863"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855973","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}

引用次数: 0

Delamination of chick cephalic neural crest cells requires an MMP14-dependent downregulation of Cadherin-6B 鸡头神经嵴细胞分层需要mmp14依赖性下调钙粘蛋白6b。

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-01 Epub Date: 2025-01-15 DOI: 10.1016/j.diff.2025.100836

Cyril Andrieu , Cathy Danesin , Audrey Montigny , Marie Rey , Klara Baqué , Anne Bibonne , Dominique Alfandari , Eric Theveneau

{"title":"Delamination of chick cephalic neural crest cells requires an MMP14-dependent downregulation of Cadherin-6B","authors":"Cyril Andrieu , Cathy Danesin , Audrey Montigny , Marie Rey , Klara Baqué , Anne Bibonne , Dominique Alfandari , Eric Theveneau","doi":"10.1016/j.diff.2025.100836","DOIUrl":"10.1016/j.diff.2025.100836","url":null,"abstract":"<div><div>Matrix Metalloproteinases (MMPs) are known for their role in matrix remodeling via their catalytic activities in the extracellular space. Interestingly, these enzymes can also play less expected roles in cell survival, polarity and motility via other substrates (e.g. receptors, chemokines), through an intracellular localization (e.g. the nucleus) or via non-catalytic functions. Most of these unconventional functions are yet to be functionally validated in a physiological context. Here, we used the delamination of the cephalic Neural Crest (NC) cells of the chicken embryo, a well described experimental model of epithelial-mesenchymal transition (EMT), to study the <em>in vivo</em> function of MMP14 (a.k.a MT1-MMP). MMP14 is a transmembrane MMP known for its importance in cell invasion and often associated with poor prognosis in cancer. We found that MMP14 is expressed and required for cephalic NC delamination. More specifically, MMP14 is necessary for the downregulation of Cadherin-6B and a co-inhibition of Cadherin-6B and MMP14 expressions is sufficient to restore NC delamination. Cadherin-6B is normally repressed by Snail2. Surprisingly, in MMP14 knockdown this lack of Cadherin-6B repression occurs in the context of a normal expression and nuclear import of Snail2. We further show that MMP14 is not detected in the nucleus and that Snail2 and MMP14 do not physically interact. These data reveals that a yet to be identified MMP14-dependent signaling event is required for the Snail2-dependent repression of Cadherin-6B. In conclusion, this work provides an <em>in vivo</em> example of atypical regulation of Cadherins by an MMP which emphasizes the importance and diversity of non-canonical functions of MMPs.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"Article 100836"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015571","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}

引用次数: 0

The fundamentals of WNT10A WNT10A 的基本原理。

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-01 Epub Date: 2025-01-30 DOI: 10.1016/j.diff.2025.100838

Erica L. Benard , Matthias Hammerschmidt

{"title":"The fundamentals of WNT10A","authors":"Erica L. Benard , Matthias Hammerschmidt","doi":"10.1016/j.diff.2025.100838","DOIUrl":"10.1016/j.diff.2025.100838","url":null,"abstract":"<div><div>Human wingless-type MMTV integration site family member 10A (<em>WNT10A</em>) is a secreted glycoprotein that is involved in signaling pathways essential to ectodermal organogenesis and tissue regeneration. <em>WNT10A</em> was first linked to human disorders in 2006, demonstrating a <em>WNT10a</em> variant to be associated with cleft lip with/without cleft palate. Numerous publications have since then identified the importance of <em>WNT10A</em> in the development of ectodermal appendages and beyond. In this review, we provide information on the structure of the <em>WNT10A</em> gene and protein, summarize its expression patterns in different animal models and in human, and describe the identified roles in tissue and organ development and repair in the different animal model organisms. We then correlate such identified functions and working mechanisms to the pathophysiology of a spectrum of human diseases and disorders that result from germline loss-of-function mutations in <em>WNT10A</em>, including ectodermal dysplasia (ED) syndromes Odonto-oncho-dermal dysplasia (OODD), Schöpf–Schulz–Passarge syndrome (SSPS), and selective tooth agenesis, as well as pathological conditions like fibrosis and carcinogenesis that can be correlated with increased WNT10A activity (Section 5).</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"Article 100838"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191238","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}

引用次数: 0