Biological Sciences Division
Published February 1, 2021 | Version v1
Journal article Open

Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length

Creators

  • 1. University of Chicago
  • 2. University at Buffalo

Description

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.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE155170 and GSE155322.

The following data sets were generated:

Mika K, Lynch VJ (2021) NCBI Gene Expression Omnibus ID GSM5100045. Mouse Endometrium Individual 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM5100045

Mika K, Lynch VJ (2021) NCBI Gene Expression Omnibus ID GSM5100046. Mouse Endometrium Individual 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM5100046

Mika K, Lynch VJ (2021) NCBI Gene Expression Omnibus ID GSM5100047. Mouse Endometrium Individual 3. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM5100047

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696515. Baboon Endometrium Individual 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696515

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GGSM4696516. Baboon Endometrium Individual 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GGSM4696516

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696517. Baboon Endometrium Individual 3. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696517

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696518. Hamster Endometrium Individual 1 Replicate 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696518

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696519. Hamster Endometrium Individual 2 Replicate 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696519

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696520. Hamster Endometrium Individual 3 Replicate 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696520

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696521. Hamster Endometrium Individual 1 Replicate 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696521

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696522. Hamster Endometrium Individual 2 Replicate 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696522

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696523. Hamster Endometrium Individual 3 Replicate 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696523

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696524. Bat Endometrium Individual 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696524

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696525. Bat Endometrium Individual 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696525

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696526. Squirrel Endometrium Individual 1. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696526

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4696527. Squirrel Endometrium Individual 2. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4696527

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699113. siRNA Ctrl_rep1a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699113

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699114. siRNA Ctrl_rep1b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699114

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699115. siRNA Ctrl_rep2a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699115

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699116. siRNA Ctrl_rep2b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699116

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699117. siRNA Ctrl_rep3a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699117

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699118. siRNA Ctrl_rep3b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699118

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699119. siRNA HAND2_rep1a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699119

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699120. siRNA HAND2_rep1b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699120

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699121. siRNA HAND2_rep2a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699121

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699122. siRNA HAND2_rep2b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699122

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699123. siRNA HAND2_rep3a. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699123

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSM4699124. siRNA HAND2_rep3b. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM4699124

Mika K, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSE155170. Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155170

Marinić M, Lynch VJ (2020) NCBI Gene Expression Omnibus ID GSE155322. Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?

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Additional details

Identifiers

DOI
10.7554/eLife.61257
Other
oai:uchicago.tind.io:9985

Funding

Burroughs Wellcome Fund
Preterm Birth Initiative
March of Dimes Foundation
UChicago-Northwestern-Duke Prematurity Research Center

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics