A5044927844- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Thyroid Disorders and Treatments
- Congenital heart defects research
- Genetic Syndromes and Imprinting
- Animal Genetics and Reproduction
- Wnt/β-catenin signaling in development and cancer
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Congenital Diaphragmatic Hernia Studies
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Pancreatic function and diabetes
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Retinal Development and Disorders
- Hematopoietic Stem Cell Transplantation
- Heart Failure Treatment and Management
- Kruppel-like factors research
- Neuroendocrine Tumor Research Advances
- Hedgehog Signaling Pathway Studies
University of Michigan
2015-2025
Michigan United
2015-2025
Justus-Liebig-Universität Gießen
2019
Universities of Giessen and Marburg Lung Center
2019
German Center for Lung Research
2019
University of Toronto
2016
Institute of Human Genetics
2012
Abstract Transcription factors and signaling pathways that regulate stem cells specialized hormone-producing in the pituitary gland have been subject of intense study yielded a mechanistic understanding organogenesis disease. However, regulation cell proliferation differentiation, heterogeneity among cells, role nonendocrine remain important, unanswered questions. Recent advances single-cell RNA sequencing (scRNAseq) technologies provide new avenues to address these We performed scRNAseq on...
The rapid advancements of single-cell RNA sequencing (scRNAseq) technology provide high-resolution views transcriptomic activity within a single cell. Most routine analyses scRNAseq data focus on individual genes; however, the one-gene-at-a-time analysis is likely to miss meaningful genetic interactions. Gene co-expression addresses this issue by identifying coordinated gene expression changes in response cellular conditions, such as developmental or temporal trajectory. Identifying...
Myelin regulatory factor (Myrf) is a critical transcription in early retinal and pigment epithelial development, human variants MYRF are cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice ( Rx > Cre fl/fl ) at 3 developmental timepoints. expressed specifically the RPE, expression abrogated eyes. scRNAseq analysis revealed loss of RPE cells all timepoints resulting from death. GO-term downregulation melanogenesis anatomic...
We report the construction of mouse full-length cDNA encyclopedia,the most extensive view a complex transcriptome,on basis preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in by Cap-Trapper,and cases,aggressively subtracted/normalized. have produced 1,442,236 successful 3′-end sequences clustered into 171,144 groups, from which 60,770 clones fully sequenced cDNAs annotated FANTOM-2 annotation. also 547,149 5′ end reads,which 124,258 groups. Altogether, these further...
Two nonallelic dwarfing mutations in mice define genes important for pituitary development and function. Mice homozygous either the Ames (df) or Snell (Pit 1dw) dwarf exhibit severe proportional dwarfism, hypothyroidism, infertility due to cytodifferentiation failure of three anterior cell types: thyrotropes, somatotropes, lactotropes. Analysis double heterozygotes mutants has provided evidence that df dw act sequentially same genetic pathway. Double had no reduction growth rate final adult...
Abstract We examined the role of WNT signaling in pituitary development by characterizing phenotype three knockout mice and assessing expression pathway components. Wnt5a mutants have expanded domains Fgf10 bone morphogenetic protein ventral diencephalon a reduced domain LHX3 Rathke's pouch. Wnt4 mildly cell differentiation, POU1F1 expression, mild anterior lobe hypoplasia. , double exhibit an additive dysmorphology Wnt6 no obvious phenotype. surveyed identified transcripts for numerous Wnts...
Mutations in PROP1 are the most common cause of hypopituitarism humans; therefore, unraveling its mechanism action is highly relevant from a therapeutic perspective. Our current understanding role pituitary gland limited to repression and activation transcription factor genes Hesx1 Pou1f1, respectively. To elucidate comprehensive PROP1-dependent gene regulatory network, we conducted genome-wide analysis DNA binding effects on expression mutant mice, mouse isolated stem cells engineered cell...
Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, high hyperopic refractive error, and frequent association angle closure glaucoma vision loss. The constitutes the extreme of hyperopia or farsightedness, common error that associated strabismus amblyopia in children. NNO1 was first mapped nanophthalmos locus. We used combined pooled exome sequencing strong linkage data large family to map this locus identify canonical...
Mutations in the prophet of PIT1 gene (PROP1) are most common cause multiple pituitary hormone deficiency humans; however, mechanism PROP1 action is not well understood. We report that Prop1 essential for dorsally restricted expression a Groucho-related gene, transducin-like enhancer split 3 (Tle3), which encodes transcriptional corepressor. Deficiency related amino terminal (Aes), causes anomalies and growth insufficiency. TLE3 AES have been shown to interact with TCF/LEF (transcripiton...
We discovered a new spontaneous mutant allele of Npr2 named peewee (pwe) that exhibits severe disproportionate dwarfism and female infertility. The pwe phenotype is caused by four base-pair deletion in exon 3 generates premature stop codon at 313 (L313X). Npr2pwe/pwe mouse model for the human skeletal dysplasia acromesomelic dysplasia, Maroteaux type (AMDM). conducted thorough analysis reproductive tract report primary cause infertility oocyte meiotic resumption, while pituitary uterus...
Rapidly cycling fetal and neonatal hematopoietic stem cells (HSCs) generate a pool of quiescent adult HSCs after establishing hematopoiesis in the bone marrow. We report an essential role for trithorax group gene absent, small, or homeotic 1-like (Ash1l) at this developmental transition. Emergence expansion Ash1l-deficient fetal/neonatal were preserved; however, young animals, profoundly depleted. had markedly decreased quiescence reduced cyclin-dependent kinase inhibitor 1b/c (Cdkn1b/1c)...
Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels TSH-β subunit gene expression. We have previously shown that retinoid X receptor–selective (RXR-selective) ligands can suppress TSH in vivo promoter activity vitro. The RXR-γ isotype has limited tissue distribution includes the thyrotrope cells anterior pituitary gland. In this study, we performed a detailed analysis mice lacking for isotype. These had significantly...
Abstract Background Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes with CH, but a vast majority of CH cases lack genetic diagnosis. Whole exome whole genome sequencing patients identifies sequence variants known to new candidate genes, many these uncertain significance (VUS). Methods The International Mouse Phenotyping Consortium...
Chromatin remodeling influences gene expression in developing and adult organisms. Active repressive marks of histone methylation dictate the embryonic boundaries developmentally regulated genes, including Hox cluster. Drosophila ash1 (absent, small or homeotic discs 1) encodes a methyltransferase essential for regulation that interacts genetically with other members trithorax group (TrxG). While mammalian mixed lineage leukemia (Mll) family TrxG genes have roles expression, little is known...
Myelin Regulatory Factor (MYRF) regulates retinal pigment epithelial (RPE) development and variants in the C-terminus are linked to isolated nanophthalmos, while loss-of-function cause syndromic disease. To define molecular mechanism of this discrepancy, vitro animal studies were performed on a pathogenic C-terminal variant (p.Gly1126fs30* or dG-MYRF). ARPE-19 cells transduced with dG-MYRF revealed reduced target gene expression compared WT-MYRF, steady state levels MYRF cleavage product,...
Abstract The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes hormones in response to hypothalamic input, end organ feedback, diurnal cues. mechanisms by which stem cells are recruited proliferate, maintain quiescence, or differentiate into specific cell types, especially thyrotropes, not well understood. We used single-cell RNA sequencing juvenile P7 mouse identify novel factors populations,...
The histone methyltransferase ASH1L plays a crucial role in regulating gene expression across various organ systems during development, yet its brain development remains largely unexplored. Over 130 individuals with autism harbour heterozygous loss-of-function variants, and population studies confirm it as high-risk gene. Previous on Ash1 l deficient mice have reported autistic-like behaviours provided insights into the underlying neuropathophysiology. In this study, we used cre-inducible...