RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy
Abstract Various types of progenitors initiate individual organ formation and their crosstalk orchestrates morphogenesis for the entire embryo. Here we show that progenitor exosomal communication across embryonic organs occurs in normal development and is altered in embryos of diabetic pregnancy. En...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-022-03614-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331658819371008 |
|---|---|
| author | Songying Cao Yanqing Wu E. Albert Reece Cheng Xu Wei-Bin Shen Sunjay Kaushal Peixin Yang |
| author_facet | Songying Cao Yanqing Wu E. Albert Reece Cheng Xu Wei-Bin Shen Sunjay Kaushal Peixin Yang |
| author_sort | Songying Cao |
| collection | DOAJ |
| description | Abstract Various types of progenitors initiate individual organ formation and their crosstalk orchestrates morphogenesis for the entire embryo. Here we show that progenitor exosomal communication across embryonic organs occurs in normal development and is altered in embryos of diabetic pregnancy. Endoderm fibroblast growth factor 2 (FGF2) stimulates mesoderm Flk-1+ vascular progenitors to produce exosomes containing the anti-stress protein Survivin. These exosomes act on neural stem cells of the neuroepithelium to facilitate neurulation by inhibiting cellular stress and apoptosis. Maternal diabetes causes Flk-1+ progenitor dysfunction by suppressing FGF2 through DNA hypermethylation. Restoring endoderm FGF2 prevents diabetes-induced survivin reduction in Flk-1+ progenitor exosomes. Transgenic Survivin expression in Flk-1+ progenitors or in utero delivery of survivin-enriched exosomes restores cellular homeostasis and prevents diabetes-induced neural tube defects (NTDs), whereas inhibiting exosome production induces NTDs. Thus, functional inter-organ communication via Flk-1 exosomes is vital for neurulation and its disruption leads to embryonic anomalies. |
| format | Article |
| id | doaj-art-d01fdc8c2bdf4fec95cc3018da8cf37b |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-d01fdc8c2bdf4fec95cc3018da8cf37b2025-08-20T03:46:27ZengNature PortfolioCommunications Biology2399-36422022-07-015111610.1038/s42003-022-03614-3RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancySongying Cao0Yanqing Wu1E. Albert Reece2Cheng Xu3Wei-Bin Shen4Sunjay Kaushal5Peixin Yang6Department of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineDepartment of Surgery, University of Maryland School of MedicineDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of MedicineAbstract Various types of progenitors initiate individual organ formation and their crosstalk orchestrates morphogenesis for the entire embryo. Here we show that progenitor exosomal communication across embryonic organs occurs in normal development and is altered in embryos of diabetic pregnancy. Endoderm fibroblast growth factor 2 (FGF2) stimulates mesoderm Flk-1+ vascular progenitors to produce exosomes containing the anti-stress protein Survivin. These exosomes act on neural stem cells of the neuroepithelium to facilitate neurulation by inhibiting cellular stress and apoptosis. Maternal diabetes causes Flk-1+ progenitor dysfunction by suppressing FGF2 through DNA hypermethylation. Restoring endoderm FGF2 prevents diabetes-induced survivin reduction in Flk-1+ progenitor exosomes. Transgenic Survivin expression in Flk-1+ progenitors or in utero delivery of survivin-enriched exosomes restores cellular homeostasis and prevents diabetes-induced neural tube defects (NTDs), whereas inhibiting exosome production induces NTDs. Thus, functional inter-organ communication via Flk-1 exosomes is vital for neurulation and its disruption leads to embryonic anomalies.https://doi.org/10.1038/s42003-022-03614-3 |
| spellingShingle | Songying Cao Yanqing Wu E. Albert Reece Cheng Xu Wei-Bin Shen Sunjay Kaushal Peixin Yang RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy Communications Biology |
| title | RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| title_full | RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| title_fullStr | RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| title_full_unstemmed | RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| title_short | RETRACTED ARTICLE: Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| title_sort | retracted article functional cargos of exosomes derived from flk 1 vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy |
| url | https://doi.org/10.1038/s42003-022-03614-3 |
| work_keys_str_mv | AT songyingcao retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT yanqingwu retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT ealbertreece retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT chengxu retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT weibinshen retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT sunjaykaushal retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy AT peixinyang retractedarticlefunctionalcargosofexosomesderivedfromflk1vascularprogenitorsenableneurulationandameliorateembryonicanomaliesindiabeticpregnancy |