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| Status |
Public on May 18, 2023 |
| Title |
CITED2 is a conserved regulator of deep placentation (Rat II) |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Establishment of the hemochorial placentation site requires the exodus of trophoblast cells from the placenta and their transformative actions on the uterine vasculature, which is a critical but poorly understood developmental process. CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl terminal domain 2 (CITED2) is a member of the CITED protein family of co-regulators and has been shown to possess roles in embryogenesis, including placenta development. We examined the involvement of CITED2 in the rat, which exhibits deep hemochorial placentation, a feature it shares with the human. CITED2 is distinctively expressed in the junctional zone compartment of the rat placentation site and in intrauterine invasive trophoblast cells. Homozygous disruption of the rat Cited2 locus resulted in placental and fetal growth restriction and abnormalities in heart and lung development, which are also characteristic of the CITED deficient mouse model. However, other features of the mouse Cited2 null phenotype, including exencephaly, adrenal gland agenesis, and prenatal lethality were not associated with CITED2 deficiency in the rat. Trophoblast-specific lentiviral CITED2 knockdown in the rat yielded a growth arrested placental phenotype. Smaller Cited2 null placentas were associated with a growth restricted junctional zone and coincided with a delay in intrauterine trophoblast cell invasion. Invasive trophoblast cells arise from the junctional zone. Transcriptomes of the junctional zone, the invasive trophoblast cell lineage, and differentiating trophoblast stem cells were affected by CITED2 disruption, as were placental adaptations to hypoxia and exposure to viral mimetics. Evidence for the conservation of CITED2 expression in human placental tissue and conserved actions in invasive/extravillous trophoblast cell development were demonstrated. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.
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| Overall design |
Rat placental junctional zone tissues were dissected on gd14.5 from heterozygous breeding of Cited2 mutant rats. Dissected junctional zone compartments from wild type and Cited2 null fetuses were snap-frozen in liquid nitrogen and stored at -80°C until processing for RNA isolation. 4 samples for wild type and 4 samples for null junctional zone tisue was analyzed.
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| Contributor(s) |
Marija K, Iqbal K, Pramod D, Soares MJ |
| Citation(s) |
36626551 |
| |
| Submission date |
May 05, 2022 |
| Last update date |
May 18, 2023 |
| Contact name |
Khursheed Iqbal |
| E-mail(s) |
kiqbal@kumc.edu
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| Phone |
913 588 5690
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| Organization name |
University of Kansas Medical Center
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| Department |
Pathology
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| Street address |
3901 Rainbow Blvd
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| City |
Kansas City |
| State/province |
Kansas |
| ZIP/Postal code |
66160 |
| Country |
USA |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE202339 |
CITED2 is a conserved regulator of deep placentation |
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| Relations |
| BioProject |
PRJNA835484 |
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