Cells and DevelopmentPub Date : 2025-03-01Epub Date: 2024-12-27DOI: 10.1016/j.cdev.2024.203990
Lucia Leitner , Martina Schultheis , Franziska Hofstetter , Claudia Rudolf , Christiane Fuchs , Valeria Kizner , Kerstin Fiedler , Marie-Therese Konrad , Julia Höbaus , Marco Genini , Julia Kober , Elisabeth Ableitner , Teresa Gmaschitz , Diana Walder , Georg Weitzer
{"title":"An autocrine synergistic desmin-SPARC network promotes cardiomyogenesis in cardiac stem cells","authors":"Lucia Leitner , Martina Schultheis , Franziska Hofstetter , Claudia Rudolf , Christiane Fuchs , Valeria Kizner , Kerstin Fiedler , Marie-Therese Konrad , Julia Höbaus , Marco Genini , Julia Kober , Elisabeth Ableitner , Teresa Gmaschitz , Diana Walder , Georg Weitzer","doi":"10.1016/j.cdev.2024.203990","DOIUrl":"10.1016/j.cdev.2024.203990","url":null,"abstract":"<div><div>The mammalian heart contains cardiac stem cells throughout life, but it has not been possible to harness or stimulate these cells to repair damaged myocardium in vivo. Assuming physiological relevance of these cells, which have evolved and have been maintained throughout mammalian evolution, we hypothesize that cardiac stem cells may contribute to cardiomyogenesis in an unorthodox manner. Since the intermediate filament protein desmin and the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) promote cardiomyogenic differentiation during embryogenesis in a cell-autonomous and paracrine manner, respectively, we focus on their genes and employ mouse embryonic and cardiac stem cell lines as in vitro models to ask whether desmin and SPARC cooperatively influence cardiomyogenesis in cardiac stem and progenitor cells. We show that desmin also promotes cardiomyogenesis in a non-cell autonomous manner by increasing the expression and secretion of SPARC in differentiating embryonic stem cells. SPARC is also secreted by cardiac stem cells where it promotes cardiomyogenesis in an autocrine and concentration-dependent manner by upregulating the expression of myocardial transcription factors and its elicitor desmin. Desmin and SPARC interact genetically, forming a positive feedback loop and secreted autocrine and paracrine SPARC negatively affects sparc mRNA expression. Paracrine SPARC rescues cardiomyogenic desmin-haploinsufficiency in cardiac stem cells in a glycosylation-dependent manner, increases desmin expression, the phosphorylation of Smad2 and induces the expression of <em>gata4, nkx2.5</em> and <em>mef2C</em>. Demonstration that desmin-induced autocrine secretion of SPARC in cardiac stem cells promotes cardiomyogenesis raises the possibility that a physiological function of cardiac stem cells in the adult and aging heart may be the gland-like secretion of factors such as SPARC that modulate age-related and adverse environmental influences and thereby contribute to cardiac homeostasis throughout life.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203990"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2025-03-01Epub Date: 2025-02-08DOI: 10.1016/j.cdev.2025.204003
Ross E. Beaumont , Emily J. Smith , Clara David , Yasmin Z. Paterson , Elena Faull , Deborah J. Guest
{"title":"Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon","authors":"Ross E. Beaumont , Emily J. Smith , Clara David , Yasmin Z. Paterson , Elena Faull , Deborah J. Guest","doi":"10.1016/j.cdev.2025.204003","DOIUrl":"10.1016/j.cdev.2025.204003","url":null,"abstract":"<div><div>Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated following a tendon injury using both 2-dimensional (2D) and 3-dimensional (3D) in vitro wound models.</div><div>We demonstrated that in 2D proliferation assays, the responses of fetal and adult tenocytes to the factors tested are more similar to each other than to ESC-tenocytes. However, in 2D migration assays, fetal tenocytes have similarities to both adult and ESC-tenocytes. In 3D wound closure assays the response of fetal tenocytes also appears to be intermediary between adult and ESC-tenocytes. We further demonstrated that while TGFβ3 increases 3D gel contraction and wound healing by adult and fetal tenocytes, FGF2 results in a significant inhibition by adult cells.</div><div>In conclusion, our findings suggest that differential cellular responses to the factors upregulated following a tendon injury may be involved in determining if tendon repair or regeneration subsequently occurs. Understanding the mechanisms behind these responses is required to inform the development of cell-based therapies to improve tendon regeneration.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 204003"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2025-03-01Epub Date: 2025-01-27DOI: 10.1016/j.cdev.2025.203997
Manuel Zúniga-García , Juan Rafael Riesgo-Escovar
{"title":"fos genes in mainly invertebrate model systems: A review of commonalities and some diversities","authors":"Manuel Zúniga-García , Juan Rafael Riesgo-Escovar","doi":"10.1016/j.cdev.2025.203997","DOIUrl":"10.1016/j.cdev.2025.203997","url":null,"abstract":"<div><div><em>fos</em> genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous <em>GCN4</em> gene is required to mediate “emergency” situations like nutrient deprivation and the unfolded protein response. The <em>C. elegans</em> homolog <em>fos-1</em> is required for reproduction and vulval development, as well as in adult homeostasis. In <em>Drosophila melanogaster</em>, there is also a sole <em>fos</em> homolog: the gene <em>kayak</em>, with five isoforms<em>.</em> The <em>kayak</em> locus has been studied in detail. It was originally described as embryonic lethal with a “dorsal open” phenotype. Since then, <em>kayak</em> has been shown to be required for oocyte maturation and as a source for piRNA; for early dorsoventral specification, macrophage function, dorsal closure, endoderm differentiation, and finally during metamorphosis in wing and eye-antennal development. In mammals there are multiple <em>fos</em> loci, each one with alternative splicing giving rise to multiple isoforms. Overall, mammalian <em>fos</em> genes are required for bone, cartilage and tooth formation, and in some instances for placental angiogenesis and retinal function. We review here mainly what is known about <em>fos</em> function in invertebrate model systems, especially during embryogenesis. We propose that <em>fos</em> genes, evolutionarily conserved transcription factors, evolved early during eukaryotic development, and from its inception as part of an environmental stress response machinery, were co-opted several times during development to regulate processes that may require similar cellular responses.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203997"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2025-03-01Epub Date: 2024-12-19DOI: 10.1016/j.cdev.2024.203989
Steven J. Chisolm , Emily Guo , Vignesh Subramaniam , Kyle D. Schulze , Thomas E. Angelini
{"title":"Transitions between cooperative and crowding-dominated collective motion in non-jammed MDCK monolayers","authors":"Steven J. Chisolm , Emily Guo , Vignesh Subramaniam , Kyle D. Schulze , Thomas E. Angelini","doi":"10.1016/j.cdev.2024.203989","DOIUrl":"10.1016/j.cdev.2024.203989","url":null,"abstract":"<div><div>Transitions between solid-like and fluid-like states in living tissues have been found in steps of embryonic development and in stages of disease progression. Our current understanding of these transitions has been guided by experimental and theoretical investigations focused on how motion becomes arrested with increased mechanical coupling between cells, typically as a function of packing density or cell cohesiveness. However, cells actively respond to externally applied forces by contracting after a time delay, so it is possible that at some packing densities or levels of cell cohesiveness, mechanical coupling stimulates cell motion instead of suppressing it. Here we report our findings that at low densities and within multiple ranges of cell cohesiveness, cell migration speeds increase with these measures of mechanical coupling. Our observations run counter to our intuition that cell motion will be suppressed by increasingly packing or sticking cells together and may provide new insight into biological processes involving motion in dense cell populations.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203989"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2025-03-01Epub Date: 2025-01-03DOI: 10.1016/j.cdev.2025.203994
Yasir Suhail , Yamin Liu , Junaid Afzal , Wenqiang Du , Paul Robson , Ashkan Novin , Ramalakshmi Ramasamy , Kshitiz
{"title":"Extravillous trophoblasts reverse the decidualization induced increase in matrix production by secreting TGFβ antagonists Emilin-1 and Gremlin-1","authors":"Yasir Suhail , Yamin Liu , Junaid Afzal , Wenqiang Du , Paul Robson , Ashkan Novin , Ramalakshmi Ramasamy , Kshitiz","doi":"10.1016/j.cdev.2025.203994","DOIUrl":"10.1016/j.cdev.2025.203994","url":null,"abstract":"<div><div>The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma. On the placental side, a new trophoblast cell type in great apes has recently evolved, called extravillous trophoblast (EVT), with an exceptionally high invasive capability. Using HTR8, and differentiated EVTs from trophectodermal stem cells, we show that EVTs partly counter decidual myofibroblast activation derived defenses. This reversal in decidual defenses is achieved by secreted antagonists of Transforming Growth Factor β/Bone morphogenic pathway, specifically Emilin-1 and Gremlin-1. Emilin-1 and Gremlin-1 reverse TGFβ activation in decidual cells, reducing high collagen production, and expression of genes associated with myofibroblast transformation. We also show that these secreted TGFβ antagonists can functionally reverse acquired decidual resistance to trophoblast invasion. As our work highlights new mechanisms evolved by trophoblasts to regulate stromal invasibility, it has broader implications in other invasive processes, including wound healing, and cancer metastasis.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203994"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Schwann cells have a limited window of time in which to initiate myelination signaling during early migration in vivo","authors":"Océane El-Hage , Aya Mikdache , Marie-José Boueid , Cindy Degerny , Marcel Tawk","doi":"10.1016/j.cdev.2024.203993","DOIUrl":"10.1016/j.cdev.2024.203993","url":null,"abstract":"<div><div>The temporal control of mitotic exit of individual Schwann cells (SCs) is essential for radial sorting and peripheral myelination. However, it remains unknown when, during their multiple rounds of division, SCs initiate myelin signaling <em>in vivo</em>. By manipulating SC division during development, we report that when SCs skip their division during migration, but not during radial sorting, they fail to myelinate peripheral axons. This coincides with a sharp decrease in Laminin expression within the posterior lateral line nerve. Interestingly, elevating cAMP levels or forcing Laminin 2 expression within individual SCs restore their ability to myelinate, despite missing mitosis during migration. Our results demonstrate a limited time window during which migrating SCs initiate Laminin expression to gradually activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages <em>in vivo</em>.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203993"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2024-12-01Epub Date: 2024-11-19DOI: 10.1016/j.cdev.2024.203976
Xinlei Liu , Sijie Xie , Xiaoxue Jiang , Shuting Song, Liyan Wang, Shujie Li, Dongdong Lu
{"title":"LUC7L2 accelerates the growth of liver cancer cells by enhancing DNA damage repair via RRAS","authors":"Xinlei Liu , Sijie Xie , Xiaoxue Jiang , Shuting Song, Liyan Wang, Shujie Li, Dongdong Lu","doi":"10.1016/j.cdev.2024.203976","DOIUrl":"10.1016/j.cdev.2024.203976","url":null,"abstract":"<div><h3>Background & objectives</h3><div>LUC7L2 may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. However, their detailed features and regulatory mechanisms of LUC7L2 in the development of human liver cancer have not been well characterized.</div></div><div><h3>Results</h3><div>Herein, our results demonstrate that LUC7L2 promotes the proliferation of liver cancer cells <em>in vitro and</em> xenograft transplantation <em>in vivo.</em> The proliferation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (24th hour: <em>P</em> = 0.00043; 48th hour: <em>P</em> = 0.000017). The cellular colony formation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (25.18±6.94 % <em>vs</em> 67.63±9.57 %, <em>P</em> = 0.00009). The weight of transplanted tumors was significantly increased in the rLV-LUC7L2 group compared to rLV group (0.387±0.074 <em>vs</em> 0.958± 0.103 g, <em>P</em> = 0.00004). Moreover, LUC7L2 effects on epigenetic regulation based on H3K4me3 in human liver cancer cells. e,g, RRAS. Furthermore, LUC7L2 affects transcriptome and proteome in liver cancer. In particular, LUC7L2 enhances the modification ability of H3K4me3and RNAPolII on the promoter region of RRAS and then enhances the expression of RRAS in liver cancer. Strikingly, LUC7L2 increases the increases the DNA damage repair ability dependent on RRAS. Although the DNA damage repair ability was significantly increased in the rLV-LUC7L2 group compared to rLV group(1.868±0.181 <em>vs</em> 0.17±0.034, <em>P</em> = 0.0000022), it was not significantly changed in rLV-LUC7L2+rLV-shRNA RRAS group compared with rLV group(1.868±0.181 <em>vs</em> 1.798±0.313, <em>P</em> = 0.317). Importantly, LUC7L2 enhances the carcinogenic function dependent on RRAS. In particular, RRAS increased the DNA damage repair ability by enhancing the formation of DNA damage repair dependent on tri-methylation of histone H3 lysine 36 (H3K36me3).</div></div><div><h3>Conclusions</h3><div>It is implied that LUC7L2's role in liver cancer proliferation is largely dependent on RRAS. The first discovery provides a basis for the prevention and treatment of human liver cancer.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203976"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2024-12-01Epub Date: 2024-08-05DOI: 10.1016/j.cdev.2024.203943
Yi Ying Cheok , Grace Min Yi Tan , Yee Teng Chan , Suhailah Abdullah , Chung Yeng Looi , Won Fen Wong
{"title":"Podoplanin and its multifaceted roles in mammalian developmental program","authors":"Yi Ying Cheok , Grace Min Yi Tan , Yee Teng Chan , Suhailah Abdullah , Chung Yeng Looi , Won Fen Wong","doi":"10.1016/j.cdev.2024.203943","DOIUrl":"10.1016/j.cdev.2024.203943","url":null,"abstract":"<div><div>Podoplanin is a vital molecule which plays an integral part in the regulation of development, immunity, and cancer. Expression of Podoplanin is detected at different early developmental stages of mammalian embryo, and it functions to modulate morphogenesis of various organ systems. In experimental animal models of different genetic backgrounds, absence of Podoplanin results in either embryonic lethality or immediate death upon birth, suggesting the importance of the gene in early developmental processes. This review discusses the gene and protein structure of Podoplanin; and elucidates various functions of Podoplanin in different systems, including central nervous system as well as respiratory, lymphatic, and cardiovascular systems.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203943"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2024-12-01Epub Date: 2024-11-09DOI: 10.1016/j.cdev.2024.203974
Nydia Tejeda-Muñoz , Grace Binder , Kuo-Ching Mei
{"title":"Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis","authors":"Nydia Tejeda-Muñoz , Grace Binder , Kuo-Ching Mei","doi":"10.1016/j.cdev.2024.203974","DOIUrl":"10.1016/j.cdev.2024.203974","url":null,"abstract":"<div><div>Aberrations in the Wnt signaling pathway, particularly mutations in genes like APC and β-catenin, are pivotal in initiating and driving the progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays a key role in regulating Wnt signaling by controlling the activation, modulation, and secretion of essential signaling molecules that contribute to CRC progression. This review explores the connection between membrane trafficking and Wnt signaling, with a specific focus on macropinocytosis—an endocytic process involved in nutrient uptake that also plays a role in Wnt signal regulation. The relationship between Wnt signaling and macropinocytosis, critical in both embryonic development and cancer onset, reveals a new dimension for therapeutic intervention. Targeting Wnt signaling through the modulation of macropinocytosis and broader membrane trafficking pathways presents a promising therapeutic strategy, with several candidates already in early clinical trials. These emerging approaches underscore the potential of targeting Wnt and its associated membrane trafficking processes for CRC treatment, aligning with the development of innovative therapies.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203974"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells and DevelopmentPub Date : 2024-12-01Epub Date: 2024-09-05DOI: 10.1016/j.cdev.2024.203970
Bingying Liu , Siqi Ren , Hong An , Yixuan Liang , Xihui Sheng , Xiaolong Qi , Longfei Xiao , Xiangguo Wang
{"title":"Establishment of functional trophoblast organoids from trophoblast cells of bovine placenta","authors":"Bingying Liu , Siqi Ren , Hong An , Yixuan Liang , Xihui Sheng , Xiaolong Qi , Longfei Xiao , Xiangguo Wang","doi":"10.1016/j.cdev.2024.203970","DOIUrl":"10.1016/j.cdev.2024.203970","url":null,"abstract":"<div><p>The placenta is an organ that plays a vital role in successful pregnancies, and the failure of early placentation is a significant factor leading to abortion in ruminant species. However, the mechanisms involved in the development and differentiation of bovine placenta remain elusive due to the lack of suitable <em>in vitro</em> placental models. This study aimed to develop an effective method for generating the bovine functional trophoblast organoids by assembling bovine primary trophoblast cells (PBTCs) from the placenta or immortalized bovine placental trophoblast (BTCs) in a 3D culture system <em>in vitro</em>. PBTCs isolated from the 3-month-gestation placenta and BTCs rapidly proliferated and exhibited typical epithelioid morphology in the modified trophoblast organoid medium (TOM) for bovine. Furthermore, PBTCs and BTCs proliferating in the modified TOM were both CK7- and E-cadherin-positive. Both PBTCs or BTCs embedded into Matrigel droplets overlaid with modified TOM proliferated and formed trophoblast organoids after 15 days of culture. Moreover, the expression of syntrophoblast marker genes, including CD71, CD46, and chorionic somatomammotropin hormone 1 (CSH1), was detectable in both organoids derived from different types of trophoblast cells. Notably, the protein expression levels of various genes implicated in the establishment of early pregnancy in endometrial epithelium cells (EECs) was increased following coculture with bovine trophoblast organoids. Collectively, the bovine trophoblast organoids established in our study could serve as robust models for elucidating the essential physical functions of the placenta and the causes of pregnancy failures related to the placenta developmental disorders during early bovine pregnancy.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203970"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}