Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy

Songying Cao; Yanqing Wu; E. Albert Reece; Cheng Xu; Wei Bin Shen; Sunjay Kaushal; Peixin Yang

doi:10.1038/s42003-022-03614-3

Functional cargos of exosomes derived from Flk-1⁺ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy

Songying Cao, Yanqing Wu, E. Albert Reece, Cheng Xu, Wei Bin Shen, Sunjay Kaushal, Peixin Yang^*

^*Corresponding author for this work

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Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Article number	648
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03614-3
State	Published - Dec 2022

Funding

The authors thank the Office of Dietary Supplements at the NIH. We thank Hua Li for her technical support and Dr. Julie Rosen at the University of Maryland School of Medicine for critical reviewing. This study is supported by National Institutes of Health (NIH) grants R01 HL131737, R01HD100195, R01HD102206, R01DK083243, R01DK101972, and R01DK103024 and an American Diabetes Association Basic Science Award (1-13-BS-220). The authors thank the Office of Dietary Supplements at the NIH. We thank Hua Li for her technical support and Dr. Julie Rosen at the University of Maryland School of Medicine for critical reviewing. This study is supported by National Institutes of Health (NIH) grants R01 HL131737, R01HD100195, R01HD102206, R01DK083243, R01DK101972, and R01DK103024 and an American Diabetes Association Basic Science Award (1-13-BS-220).

ASJC Scopus subject areas

General Agricultural and Biological Sciences
General Biochemistry, Genetics and Molecular Biology
Medicine (miscellaneous)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s42003-022-03614-3

Cite this

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title = "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. 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.",

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AU - Shen, Wei Bin

AU - Kaushal, Sunjay

AU - Yang, Peixin

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