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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-9581055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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