Pub 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
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.
{"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}
Pub 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
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.
{"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}
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 in vivo. 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 in vivo.
{"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}
Pub 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
Background & objectives
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.
Results
Herein, our results demonstrate that LUC7L2 promotes the proliferation of liver cancer cells in vitro and xenograft transplantation in vivo. The proliferation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (24th hour: P = 0.00043; 48th hour: P = 0.000017). The cellular colony formation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (25.18±6.94 % vs 67.63±9.57 %, P = 0.00009). The weight of transplanted tumors was significantly increased in the rLV-LUC7L2 group compared to rLV group (0.387±0.074 vs 0.958± 0.103 g, P = 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 vs 0.17±0.034, P = 0.0000022), it was not significantly changed in rLV-LUC7L2+rLV-shRNA RRAS group compared with rLV group(1.868±0.181 vs 1.798±0.313, P = 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).
Conclusions
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.
{"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}
Pub 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
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.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-09DOI: 10.1016/j.cdev.2024.203974
Nydia Tejeda-Muñoz , Grace Binder , Kuo-Ching Mei
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.
{"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}
Pub 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
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 in vitro 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 in vitro. 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.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-14DOI: 10.1016/j.cdev.2024.203975
Hyung Kyu Choi, Sung-Hwan Moon
Research on early human development is crucial for understanding the origins of life and mechanisms underlying disease onset. However, these studies have significant challenges owing to ethical restrictions and technical limitations. Stem cell technology advancement has led to the development of blastoids to overcome these challenges.” Blastoids are three-dimensional structures produced by pluripotent stem cells (PSCs) that resemble the blastocyst stage of human embryos. Research on blastoids can enhance our understanding of early human development and drive innovations in regenerative medicine and disease modeling.
This review outlines the background of blastoid development and highlights the limitations of existing organoid research. It presents developments in blastoid research, from previous studies using animal models to the latest developments using human stem cell-derived blastoids in early human development studies. Additionally, this review provides a comparative analysis of the methods used to develop blastoids across various studies, evaluating their potential as ethical alternatives for regenerative medicine, human developmental biology, and embryonic research. It further assesses the ethical and social considerations surrounding blastoid research, the current strategies to address these concerns, and the potential long-term impact on science and medicine.
We aimed to provide a comprehensive understanding of the current trends in blastoid research, offer new insights into early human development, and suggest novel directions and approaches for researchers.
{"title":"Blastoid: The future of human development in the laboratory","authors":"Hyung Kyu Choi, Sung-Hwan Moon","doi":"10.1016/j.cdev.2024.203975","DOIUrl":"10.1016/j.cdev.2024.203975","url":null,"abstract":"<div><div>Research on early human development is crucial for understanding the origins of life and mechanisms underlying disease onset. However, these studies have significant challenges owing to ethical restrictions and technical limitations. Stem cell technology advancement has led to the development of blastoids to overcome these challenges.” Blastoids are three-dimensional structures produced by pluripotent stem cells (PSCs) that resemble the blastocyst stage of human embryos. Research on blastoids can enhance our understanding of early human development and drive innovations in regenerative medicine and disease modeling.</div><div>This review outlines the background of blastoid development and highlights the limitations of existing organoid research. It presents developments in blastoid research, from previous studies using animal models to the latest developments using human stem cell-derived blastoids in early human development studies. Additionally, this review provides a comparative analysis of the methods used to develop blastoids across various studies, evaluating their potential as ethical alternatives for regenerative medicine, human developmental biology, and embryonic research. It further assesses the ethical and social considerations surrounding blastoid research, the current strategies to address these concerns, and the potential long-term impact on science and medicine.</div><div>We aimed to provide a comprehensive understanding of the current trends in blastoid research, offer new insights into early human development, and suggest novel directions and approaches for researchers.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203975"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639946","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}
Pub Date : 2024-12-01Epub Date: 2024-10-18DOI: 10.1016/j.cdev.2024.203971
D. Weiss , N. Yeung , A.B. Ramachandra , J.D. Humphrey
The aorta exhibits tremendous changes in geometry, composition, and mechanical properties during postnatal development. These changes are necessarily driven by transcriptional changes, both genetically programmed and mechano-responsive, but there has not been a careful comparison of time-course changes in the transcriptional profile and biomechanical phenotype. Here, we show that the greatest period of differential gene expression in the normal postnatal mouse aorta occurs prior to weaning at three weeks of age though with important evolution of many transcripts thereafter. We identify six general temporal patterns, including transcripts that monotonically decrease to lower or increase to higher steady state values as well as those that either peak or dip prior to or near weaning. We show that diverse transcripts within individual groupings correlate well over time, and that sub-sets of these groups correlate well with the developmental progression of different biomechanical metrics that are expected to be involved in mechano-sensing. In particular, expression of genes for elastin and elastin-associated glycoproteins tend to correlate well with the ratio of systolic-to-diastolic stress whereas genes for collagen fibers correlate well with the daily rate of change of systolic stress and genes for mechano-sensing proteins tend to correlate well with the systolic stress itself. We conclude that different groupings of genes having different temporal expression patterns correlate well with different measures of the wall mechanics, hence emphasizing a need for age-dependent, gene-specific computational modeling of postnatal development.
{"title":"Transcriptional regulation of postnatal aortic development","authors":"D. Weiss , N. Yeung , A.B. Ramachandra , J.D. Humphrey","doi":"10.1016/j.cdev.2024.203971","DOIUrl":"10.1016/j.cdev.2024.203971","url":null,"abstract":"<div><div>The aorta exhibits tremendous changes in geometry, composition, and mechanical properties during postnatal development. These changes are necessarily driven by transcriptional changes, both genetically programmed and mechano-responsive, but there has not been a careful comparison of time-course changes in the transcriptional profile and biomechanical phenotype. Here, we show that the greatest period of differential gene expression in the normal postnatal mouse aorta occurs prior to weaning at three weeks of age though with important evolution of many transcripts thereafter. We identify six general temporal patterns, including transcripts that monotonically decrease to lower or increase to higher steady state values as well as those that either peak or dip prior to or near weaning. We show that diverse transcripts within individual groupings correlate well over time, and that sub-sets of these groups correlate well with the developmental progression of different biomechanical metrics that are expected to be involved in mechano-sensing. In particular, expression of genes for elastin and elastin-associated glycoproteins tend to correlate well with the ratio of systolic-to-diastolic stress whereas genes for collagen fibers correlate well with the daily rate of change of systolic stress and genes for mechano-sensing proteins tend to correlate well with the systolic stress itself. We conclude that different groupings of genes having different temporal expression patterns correlate well with different measures of the wall mechanics, hence emphasizing a need for age-dependent, gene-specific computational modeling of postnatal development.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203971"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476399","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}
Pub Date : 2024-12-01Epub Date: 2024-10-26DOI: 10.1016/j.cdev.2024.203973
Katerina Karkali, Enrique Martín-Blanco
The establishment of communication circuits requires bringing sources and targets into contact, either directly or indirectly. The Central Nervous System (CNS)'s ability to interpret the environment and generate precise responses depends on the functional efficiency of its neural network, which in turn relies on the 3D spatial organization of its constituents, mainly neurons and glia. Throughout evolution, sensory integration and motor response coordination became linked with the merging of the brain and nerve cord (NC) in the urbilaterian CNS. In most arthropods, the NC follows a specific topological plan and consists of a fixed number of neuromeres (thoracic and abdominal ganglia with commissural interconnections and a single terminal ganglion). The number, spacing, and fusion of neuromeres are species-specific and can change during embryogenesis or post-embryonic life. During Drosophila embryogenesis, the NC condenses along the Anterior-Posterior (AP) axis in a stereotypical manner, bringing neuromeres closer together. This process has revealed several key parameters, including its morphogenetic mechanics, the roles of various cellular, molecular, and structural components, and the functional purpose of its balanced design. The embryonic NC serves as a valuable model for investigating the ancient mechanisms underlying the structural organization, sensory integration, and motor coordination of the CNS. While many aspects of ganglionic fusion remain unknown, ongoing research promises to provide a more comprehensive understanding of the mechanical and evolutionary principles that govern it.
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