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| Status |
Public on Jul 28, 2020 |
| Title |
Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length |
| Organisms |
Papio anubis; Mesocricetus auratus; Mus musculus; Carollia perspicillata; Ictidomys tridecemlineatus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian (‘Placental') mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.
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| Overall design |
Multi-species RNA-Seq to identify genes expressed in the pregnant uterus
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| Contributor(s) |
Mika KM, Lynch VJ |
| Citation missing |
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| |
| Submission date |
Jul 27, 2020 |
| Last update date |
Feb 26, 2021 |
| Contact name |
Katelyn Mika |
| E-mail(s) |
[email protected], [email protected]
|
| Organization name |
University of Chicago
|
| Department |
Organismal Biology; Genetic Medicine
|
| Lab |
Shubin, Basu
|
| Street address |
1025 E. 57th Street
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
| |
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| Platforms (5)
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| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL20744 |
Illumina HiSeq 2500 (Carollia perspicillata) |
| GPL22399 |
Illumina HiSeq 2500 (Mesocricetus auratus) |
| GPL22929 |
Illumina HiSeq 2500 (Ictidomys tridecemlineatus) |
| GPL23487 |
Illumina HiSeq 2500 (Papio anubis) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA648914 |
| SRA |
SRP273714 |
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