Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms

Transcriptome-wide association analyses identify an association between ARL14EP and polycystic ovary syndrome

“…Therefore, a change in ARL14EP expression may result in changes in chromatin remodeling, and consequently, changes in FSHB expression. In line with this, recent analyses using the Single Cell Enhancer Target gene mapping (SCENT) tool, have shown that rs11031006 (the most likely causal variant identified by the study) was located in a region of open chromatin that was linked to FSHB expression, specifically in pituitary cells [45,46]. Therefore, it is possible that ARL14EPmediated chromatin remodelling may result in a change in enhancer chromatin accessibility in the pituitary, which in turn influences FSHB expression.…”

Tissue-specific enhancer-gene maps from multimodal single-cell data identify causal disease alleles

“…In a final example, we highlight the value of using SCENT to build enhancer-gene maps from disease-critical tissues. We examined the enhancer-gene map produced from single-cell multimodal pituitary data 61 to assess the 11p14.1 locus for multiple gynecological traits (endometriosis, menorrhagia, ovarian cyst and age at menopause). Our map connected rs11031006 to FSHB (follicle stimulating hormone subunit beta) ( Figure 4c ), which is specifically expressed in the pituitary 69,86 and enables ovarian folliculogenesis to the antral follicle stage 87 .…”

“…In addition, we obtained eight public data sets with 129,672 cells. In total we had data from 160,565 cells 46,[57][58][59][60][61] 1). After clustering cells and annotating them with cell labels, we applied SCENT individually to each of the cell types with n cells > 500 within each dataset to construct 23 enhancer-gene maps.…”

Cellular interactions in the pituitary stem cell niche

“…[ 131 ] Whole rat pituitary 15,876 cells from 60 × 75 day -old female rats (Combined from; separated rat anterior pituitary, separated rat intermediate lobe and posterior pituitary, and whole rat pituitary) Zhang et al . [ 121 ] Human pediatric, adult and aged pituitary 76,016 nuclei for snRNAseq 15,024 nuclei in the same-cell sn multiome (ATAC and RNA) Laporte E et al [ 122 ] Anterior pituitaries of control and mutant mice 9618 cells from control 2 × P7 mice 11,801 from mutant 2 × P7 mice …”

“…As well as unearthing cellular heterogeneity, from these types of data, we can infer cell-crosstalk based on transcript expression of known receptor-and ligandpairs. Analysis of these pairs throughout whole tissues Whole mouse pituitary 13,663 cells from 6 × 7 week male mice Fletcher et al [112] Rat anterior pituitary 6896 cells from 2 male and 2 female postpubertal rats Mayran et al [103] Mouse anterior pituitary 9269 cells from 1 male 4 month old mouse Cheung et al [110] Whole mouse pituitary 6492 cells from 1 × P4 female mutant mouse 6705 cells from 1 × P4 female control mouse Chen et al [113] Mouse intermediate and posterior pituitary lobes 528 cells from 1 × 3 month old male mouse Ho et al [114] Whole mouse pituitary 3532 cells from 1 × 13 week old virgin female 7614 cells from 2 × 13 week old lactating females 7443 cells from 4 × 8 week old male and females 2596 cells from 8 week old acromegalic female Zhang et al [108] Human fetal pituitary 4113 cells from 21 human fetuses Lopez J.P et al [115] Whole mouse pituitary 9,879 cells from 10 week-old male mice: 5 x unstressed and 5 x chronically stressed Moncho-Amor et al [116] Intermediate lobes of control and mutant mouse pituitaries 2110 cells from 3 month old control male and female mice 8832 cells from 3 month old mutant male and female mice Cui et al [117] Human neuroendocrine tumours 2679 cells from 21 human patients Ruf-Zamojski et al [70] Whole mouse pituitary 35,707 nuclei from 6 × 10-12 week old male and female mice Allensworth-James M et al [118] Whole mouse pituitary 18,301 cells from 6 x 8-week old diestrous female mice Vennekens et al [98] Anterior pituitaries of control and mutant mice 7977 cells from 9-11 weeks old control male mice 7000 cells from 9-11 weeks old mutant male mice 5278 cells from 14 month old control male mice 5860 cells from 14 month old mutant male mice Zhang et al [119] Whole chicken anterior pituitary 6733 cells from 6 male chicken and 9,919 cells from 6 female chicken both at 12 months Siddique et al [120] Whole adult teleost pituitaries 2592 cells from female teleost and 3804 cells from male teleost Fletcher et al [131] Whole rat pituitary 15,876 cells from 60 × 75 day -old female rats (Combined from; separated rat anterior pituitary, separated rat intermediate lobe and posterior pituitary, and whole rat pituitary) Zhang et al [121] Human pediatric, adult and aged pituitary 76,016 nuclei for snRNAseq 15,024 nuclei in the same-cell sn multiome (ATAC and RNA) Laporte E et al [122] Anterior pituitaries of control and mutant mice 9618 cells from control 2 × P7 mice 11,801 from mutant 2 × P7 mice was previously unachievable. In addition, the advent of single cell (or single nuclei) ATAC-seq has revolutionised the detail by which we can interrogate chromatin regulatory landscapes by measuring the...…”