scholarly journals Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms

2021 ◽  
Author(s):  
Zidong Zhang ◽  
Michel Zamojski ◽  
Gregory R Smith ◽  
Thea L Willis ◽  
Val Yianni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Age Groups ◽  
Specific Gene ◽  
Regulatory Domain ◽  
Human Stem Cell ◽  
Linear Modeling ◽  
Human Pituitary ◽  
Cell Lineages ◽  
Single Nucleus

Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a human single nucleus (sn) RNAseq and ATACseq resource from pediatric, adult, and aged pituitaries (snpituitaryatlas.princeton.edu) and characterize cell type-specific gene expression and chromatin accessibility programs for all major pituitary cell lineages. We identify uncommitted PSCs, committing progenitor cells, and sex differences. Pseudotime trajectory analysis indicates that early life PSCs are distinct from the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain accessibility sites and transcription factors (TFs) that are significantly associated with gene expression in PSCs compared to other cell types and within PSCs. Modeling the heterogeneous expression of two markers for committing cell lineages among PSCs shows significant correlation with regulatory domain accessibility for GATA3, but with TF expression for POMC. These findings characterize human stem cell lineages and reveal diverse mechanisms regulating key PSC genes.

Validation of a novel human stem cell-based gene expression assay for in vitro DART assessment

2019 ◽  
Vol 88 ◽  
pp. 18-19
Author(s):  
Peter I. Racz ◽  
Inger Brandsma ◽  
Sabine Hartvelt ◽  
Tom Zwetsloot ◽  
Giel Hendriks
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Human Stem Cell ◽  
Gene Expression Assay

Activity of metabolic enzymes and muscle-specific gene expression in parr and smolts Atlantic salmon Salmo salar L. of different age groups

2017 ◽  
Vol 43 (4) ◽  
pp. 1117-1130 ◽  
Author(s):  
Maria V. Churova ◽  
Olga V. Meshcheryakova ◽  
Aleksey E. Veselov ◽  
Denis A. Efremov ◽  
Nina N. Nemova
Keyword(s):  
Gene Expression ◽  
Atlantic Salmon ◽  
Salmo Salar ◽  
Age Groups ◽  
Metabolic Enzymes ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Atlantic Salmon Salmo Salar

Disparate differentiation in hemopoietic colonies derived from human paired progenitors

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 327-332 ◽  
Author(s):  
AG Leary ◽  
LC Strauss ◽  
CI Civin ◽  
M Ogawa
Keyword(s):  
Stem Cell ◽  
Blood Cells ◽  
Individual Cell ◽  
Stem Cell Differentiation ◽  
Cellular Composition ◽  
Human Stem Cell ◽  
Cell Lineages ◽  
Daughter Cells ◽  
Cord Blood Cells ◽  
The Individual

Abstract We analyzed the differentiation of hemopoietic colonies derived from human paired daughter cells. Candidate progenitor cells were isolated by use of a micromanipulation technique from cultures of My-10 antigen- positive cord blood cells. Then nine to 36 hours later, the paired daughter cells were separated with a micromanipulator and allowed to form colonies in methylcellulose medium containing erythropoietin, phytohemagglutinin leukocyte-conditioned medium, and platelet-poor plasma. The cellular composition of the colonies was determined by differentiating all of the cells of the May-Grunwald-Giemsa-stained preparation. Of a total of 75 evaluable pairs of colonies, 35 consisted of 28 types of disparate pairs revealing nonhomologous lineage combinations. Forty pairs were homologous in lineage expression. However, the proportions of the individual cell lineages were significantly different in the members of some of the homologous pairs. Some pairs revealed significant differences in colony size. These observations are similar to those reported for murine paired progenitors and are consistent with the stochastic model of human stem cell differentiation.

scholarly journals Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

2020 ◽  
Author(s):  
Jonathan Lenz ◽  
Robert Liefke ◽  
Julianne Funk ◽  
Samuel Shoup ◽  
Andrea Nist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cell ◽  
Specific Gene ◽  
Cell Cycle Regulators ◽  
Cell Type ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Specific Gene Expression ◽  
Cell Type Specific

AbstractThe generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.

scholarly journals m6A is required for resolving progenitor identity during planarian stem cell differentiation

2021 ◽  
Author(s):  
Yael Dagan ◽  
Yarden Yesharim ◽  
Ashley R. Bonneau ◽  
Schraga Schwartz ◽  
Peter W. Reddien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Histone Variants ◽  
Cell Lineages ◽  
Base Modification ◽  
Undifferentiated Cells ◽  
Chromatin Modifying Complex ◽  
Transcriptional State

Regeneration requires accurate production of missing cell lineages. Cell production is driven by changes to gene expression, which is shaped by multiple layers of regulation. Here, we find that the ubiquitous mRNA base-modification, m6A, is required for proper cell fate choice and cellular maturation in planarian stem cells (neoblasts). We mapped m6A-enriched regions in 7,600 planarian genes, and found that perturbation of the m6A pathway resulted in progressive deterioration of tissues and death. Using single cell RNA sequencing of >20,000 cells following perturbation of the pathway, we discovered that m6A negatively regulates transcription of histone variants, and that inhibition of the pathway resulted in accumulation of undifferentiated cells throughout the animal in an abnormal transcriptional state. Analysis of >1000 planarian gene expression datasets revealed that the inhibition of the chromatin modifying complex NuRD had almost indistinguishable consequences, unraveling an unappreciated link between m6A and chromatin modifications. Our findings reveal that m6A is critical for planarian stem cell homeostasis and gene regulation in regeneration.

scholarly journals Multiscale 3D Genome Reorganization during Skeletal Muscle Stem Cell Lineage Progression and Muscle Aging

2021 ◽  
Author(s):  
Huating WANG ◽  
Yu Zhao ◽  
Yingzhe Ding ◽  
Liangqiang He ◽  
Yuying Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Muscle Stem Cell ◽  
3D Genome ◽  
Chromatin Looping ◽  
Early Activation

Abstract 3D genome rewiring is known to influence spatiotemporal expression of lineage-specific genes and cell fate transition during stem cell differentiation and aging processes. Yet it is unknown how 3D architecture remodels and orchestrates transcriptional changes during skeletal muscle stem cell (also called satellite cell, SC) activation, proliferation and differentiation course. Here, using in situ Hi-C we comprehensively map the 3D genome topology reorganization at multiscale levels during mouse SC lineage progression and integrate with transcriptional and chromatin signatures to elucidate how 3D genome rewiring dictates gene expression program. Specifically, rewiring at compartment level is most pronounced when SC becomes activated. Striking loss in TAD border insulation and chromatin looping also occurs during early activation process. Meanwhile, TADs can also form TAD clusters and super-enhancer containing TAD clusters orchestrate stage-specific gene expression during SC early activation. Furthermore, we elucidate 3D chromatin regulation of key transcription factor, PAX7 and identify cis-regulatory elements that are crucial for local chromatin architecture and Pax7 expression. Lastly, 3D genome remodeling is profiled in SCs isolated from naturally aging mice, unveiling that geriatric SCs display a prominent gain in long-range contacts and loss of TAD border insulation. Genome compartmentalization and chromatin looping are evidently altered in aged SC while geriatric SC display a more prominent loss in strength of TAD borders. Together, our results implicate 3D chromatin extensively reorganizes at multiple architectural levels and underpin the transcriptome remodeling during SC lineage development and SC aging.

scholarly journals Differential Gene Expression in Articular Cartilage and Subchondral Bone of Neonatal and Adult Horses

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 745
Author(s):  
Ann M. Kemper ◽  
Jenny Drnevich ◽  
Molly E. McCue ◽  
Annette M. McCoy
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Neural Development ◽  
Disease Risk ◽  
Differential Expression Analysis ◽  
Age Groups ◽  
Differentially Expressed ◽  
Tissue Type ◽  
Specific Gene

Skeletogenesis is complex and incompletely understood. Derangement of this process likely underlies developmental skeletal pathologies. Examination of tissue-specific gene expression may help elucidate novel skeletal developmental pathways that could contribute to disease risk. Our aim was to identify and functionally annotate differentially expressed genes in equine neonatal and adult articular cartilage (AC) and subchondral bone (SCB). RNA was sequenced from healthy AC and SCB from the fetlock, hock, and stifle joints of 6 foals (≤4 weeks of age) and six adults (8–12 years of age). There was distinct clustering by age and tissue type. After differential expression analysis, functional annotation and pathway analysis were performed using PANTHER and Reactome. Approximately 1115 and 3574 genes were differentially expressed between age groups in AC and SCB, respectively, falling within dozens of overrepresented gene ontology terms and enriched pathways reflecting a state of growth, high metabolic activity, and tissue turnover in the foals. Enriched pathways were dominated by those related to extracellular matrix organization and turnover, and cell cycle and signal transduction. Additionally, we identified enriched pathways related to neural development and neurotransmission in AC and innate immunity in SCB. These represent novel potential mechanisms for disease that can be explored in future work.

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