Gene Regulatory Networks Orchestrating B Cell Fate Specification, Commitment, and Differentiation

2005 ◽  
pp. 1-14 ◽  
Author(s):  
K. L. Medina ◽  
H. Singh
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Gene Regulatory

scholarly journals Unraveling Root Development Through Single-Cell Omics and Reconstruction of Gene Regulatory Networks

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Serrano-Ron ◽  
Javier Cabrera ◽  
Pablo Perez-Garcia ◽  
Miguel A. Moreno-Risueno
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Root Development ◽  
Regulatory Networks ◽  
Primary Root ◽  
Cell Fate Specification ◽  
Rna Seq ◽  
Fate Specification ◽  
Gene Regulatory

Over the last decades, research on postembryonic root development has been facilitated by “omics” technologies. Among these technologies, microarrays first, and RNA sequencing (RNA-seq) later, have provided transcriptional information on the underlying molecular processes establishing the basis of System Biology studies in roots. Cell fate specification and development have been widely studied in the primary root, which involved the identification of many cell type transcriptomes and the reconstruction of gene regulatory networks (GRN). The study of lateral root (LR) development has not been an exception. However, the molecular mechanisms regulating cell fate specification during LR formation remain largely unexplored. Recently, single-cell RNA-seq (scRNA-seq) studies have addressed the specification of tissues from stem cells in the primary root. scRNA-seq studies are anticipated to be a useful approach to decipher cell fate specification and patterning during LR formation. In this review, we address the different scRNA-seq strategies used both in plants and animals and how we could take advantage of scRNA-seq to unravel new regulatory mechanisms and reconstruct GRN. In addition, we discuss how to integrate scRNA-seq results with previous RNA-seq datasets and GRN. We also address relevant findings obtained through single-cell based studies and how LR developmental studies could be facilitated by scRNA-seq approaches and subsequent GRN inference. The use of single-cell approaches to investigate LR formation could help to decipher fundamental biological mechanisms such as cell memory, synchronization, polarization, or pluripotency.

scholarly journals Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina

Cell Reports ◽  
2021 ◽  
Vol 37 (7) ◽  
pp. 109994
Author(s):  
Pin Lyu ◽  
Thanh Hoang ◽  
Clayton P. Santiago ◽  
Eric D. Thomas ◽  
Andrew E. Timms ◽  
...  
Keyword(s):  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Specification ◽  
Temporal Patterning ◽  
Fate Specification ◽  
Mammalian Retina ◽  
Gene Regulatory

scholarly journals Gene regulatory networks controlling temporal patterning, neurogenesis and cell fate specification in the mammalian retina.

2021 ◽  
Author(s):  
Pin Lyu ◽  
Thanh Hoang ◽  
Clayton P Santiago ◽  
Eric Thomas ◽  
Andrew Timms ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Specification ◽  
Cell Type ◽  
Temporal Patterning ◽  
Fate Specification ◽  
Expression Of Genes ◽  
Gene Regulatory

Gene regulatory networks (GRNs), consisting of transcription factors and their target cis-regulatory sequences, control neurogenesis and cell fate specification in the developing central nervous system, but their organization is poorly characterized. In this study, we performed integrated scRNA-seq and scATAC-seq analysis from both mouse and human retina to profile dynamic changes in gene expression, chromatin accessibility and transcription factor footprinting during retinal neurogenesis. We identified multiple interconnected, evolutionarily-conserved GRNs consisting of cell type-specific transcription factors that both activate expression of genes within their own network and often inhibit expression of genes in other networks. These GRNs control state transitions within primary retinal progenitors that underlie temporal patterning, regulate the transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirmed the prediction of this analysis that the NFI transcription factors Nfia, Nfib, and Nfix selectively activate expression of genes that promote late-stage temporal identity in primary retinal progenitors. We also used GRNs to identify additional transcription factors that selectively promote (Insm1/2) and inhibit (Tbx3, Tcf7l1/2) rod photoreceptor specification in postnatal retina. This study provides an inventory of cis- and trans-acting factors that control retinal development, identifies transcription factors that control the temporal identity of retinal progenitors and cell fate specification, and will potentially help guide cell-based therapies aimed at replacing retinal neurons lost due to disease.

scholarly journals GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mika J. Välimäki ◽  
Robert S. Leigh ◽  
Sini M. Kinnunen ◽  
Alexander R. March ◽  
Ana Hernández de Sande ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Reporter Gene ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Decisions ◽  
Dual Reporter ◽  
Gene Regulatory ◽  
Reporter Gene Assays

AbstractBackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.

scholarly journals Short-Circuiting Gene Regulatory Networks: Origins of B Cell Lymphoma

2015 ◽  
Vol 31 (12) ◽  
pp. 720-731 ◽  
Author(s):  
Olivia I. Koues ◽  
Eugene M. Oltz ◽  
Jacqueline E. Payton
Keyword(s):  
B Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Regulatory
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