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Identification of Biomarkers Controlling Cell Fate In Blood Cell Development

A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are no...

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Autores principales: Nazarieh, Maryam, Hoeppner, Marc, Helms, Volkhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581055/
https://www.ncbi.nlm.nih.gov/pubmed/36303754
http://dx.doi.org/10.3389/fbinf.2021.653054
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author Nazarieh, Maryam
Hoeppner, Marc
Helms, Volkhard
author_facet Nazarieh, Maryam
Hoeppner, Marc
Helms, Volkhard
author_sort Nazarieh, Maryam
collection PubMed
description A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their corresponding target genes. A possible step forward in this case is provided by the increasing amount of expression data, as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators excert along the differentiation path of cell lineages. Based on such simple patterns, we identified cell state-specific marker genes and extracted TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific “key player” genes yielded a distinct peaking pattern for each lineage that was used to identify further genes in the dataset which behave similarly. Incorporating the set of TFs that regulate these genes led to a set of stage-specific regulators that control the biological process of cell fate. As proof of concept, we considered two expression datasets covering key differentiation events in blood cell formation of mice.
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spelling pubmed-95810552022-10-26 Identification of Biomarkers Controlling Cell Fate In Blood Cell Development Nazarieh, Maryam Hoeppner, Marc Helms, Volkhard Front Bioinform Bioinformatics A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their corresponding target genes. A possible step forward in this case is provided by the increasing amount of expression data, as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators excert along the differentiation path of cell lineages. Based on such simple patterns, we identified cell state-specific marker genes and extracted TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific “key player” genes yielded a distinct peaking pattern for each lineage that was used to identify further genes in the dataset which behave similarly. Incorporating the set of TFs that regulate these genes led to a set of stage-specific regulators that control the biological process of cell fate. As proof of concept, we considered two expression datasets covering key differentiation events in blood cell formation of mice. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC9581055/ /pubmed/36303754 http://dx.doi.org/10.3389/fbinf.2021.653054 Text en Copyright © 2021 Nazarieh, Hoeppner and Helms. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioinformatics
Nazarieh, Maryam
Hoeppner, Marc
Helms, Volkhard
Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title_full Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title_fullStr Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title_full_unstemmed Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title_short Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
title_sort identification of biomarkers controlling cell fate in blood cell development
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581055/
https://www.ncbi.nlm.nih.gov/pubmed/36303754
http://dx.doi.org/10.3389/fbinf.2021.653054
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