Examining Sex Differences in the Human Placental Transcriptome During the First Fetal Androgen Peak.

Sex differences in human placenta exist from early pregnancy to term, however, it is unclear whether these differences are driven solely by sex chromosome complement or are subject to differential sex hormonal regulation. Here, we survey the human chorionic villus (CV) transcriptome for sex-linked signatures from 11 to 16 gestational weeks, corresponding to the first window of increasing testis-derived androgen production in male fetuses. Illumina HiSeq RNA sequencing was performed on Lexogen Quantseq 3' libraries derived from CV biopsies (n = 11 females, n = 12 males). Differential expression (DE) was performed to identify sex-linked transcriptional signatures, followed by chromosome mapping, pathway analysis, predicted protein interaction, and post-hoc linear regressions to identify transcripts that trend over time. We observe 322 transcripts DE between male and female CV from 11 to 16 weeks, with 22 transcripts logFC > 1. Contrary to our predictions, the difference between male and female expression of DE autosomal genes was more pronounced at the earlier gestational ages. In females, we found selective upregulation of extracellular matrix components, along with a number of X-linked genes. In males, DE transcripts centered on chromosome 19, with mitochondrial, immune, and pregnancy maintenance-related transcripts upregulated. Among the highest differentially expressed autosomal genes were CCRL2, LGALS13, and LGALS14, which are known to regulate immune cell interactions. Our results provide insight into sex-linked gene expression in late first and early second trimester developing human placenta and lay the groundwork to understand the mechanistic origins of sex differences in prenatal development.

16p11.2 microdeletion imparts transcriptional alterations in human iPSC-derived models of early neural development.

Microdeletions and microduplications of the 16p11.2 chromosomal locus are associated with syndromic neurodevelopmental disorders and reciprocal physiological conditions such as macro/microcephaly and high/low body mass index. To facilitate cellular and molecular investigations into these phenotypes, 65 clones of human induced pluripotent stem cells (hiPSCs) were generated from 13 individuals with 16p11.2 copy number variations (CNVs). To ensure these cell lines were suitable for downstream mechanistic investigations, a customizable bioinformatic strategy for the detection of random integration and expression of reprogramming vectors was developed and leveraged towards identifying a subset of 'footprint'-free hiPSC clones. Transcriptomic profiling of cortical neural progenitor cells derived from these hiPSCs identified alterations in gene expression patterns which precede morphological abnormalities reported at later neurodevelopmental stages. Interpreting clinical information-available with the cell lines by request from the Simons Foundation Autism Research Initiative-with this transcriptional data revealed disruptions in gene programs related to both nervous system function and cellular metabolism. As demonstrated by these analyses, this publicly available resource has the potential to serve as a powerful medium for probing the etiology of developmental disorders associated with 16p11.2 CNVs.

Gradient phonological inconsistency affects vocabulary learning.

Learners frequently experience phonologically inconsistent input, such as exposure to multiple accents. Yet, little is known about the consequences of phonological inconsistency for language learning. The current study examines vocabulary acquisition with different degrees of phonological inconsistency, ranging from no inconsistency (e.g., both talkers call a picture /vig/) to mild but detectable inconsistency (e.g., one talker calls a picture a /vig/, and the other calls it a /vIg/), up to extreme inconsistency (e.g., the same picture is both a /vig/ and a /dIdʒ/). Previous studies suggest that learners readily extract consistent phonological patterns, given variable input. However, in Experiment 1, adults acquired phonologically inconsistent vocabularies more slowly than phonologically consistent ones. Experiment 2 examined whether word-form inconsistency alone, without phonological competition, was a source of learning difficulty. Even without phonological competition, listeners learned faster in 1 accent than in 2 accents, but they also learned faster in 2 accents (/vig/ = /vIg/) than with completely different labels (/vig/ = /dIdʒ/). Overall, results suggest that learners exposed to multiple accents may experience difficulty learning when 2 forms mismatch by more than 1 phonological feature, plus increased phonological competition due to a greater number of word forms. Implications for learning from variable input are discussed.