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Transcriptome-wide profiling and posttranscriptional analysis of hematopoietic stem/progenitor cell differentiation toward myeloid commitment

Klimmeck, Daniel; Cabezas-Wallscheid, Nina; Reyes, Alejandro; von Paleske, Lisa; Renders, Simon; Hansson, Jenny LU ; Krijgsveld, Jeroen; Huber, Wolfgang and Trumpp, Andreas (2014) In Stem Cell Reports 3(5). p.75-858
Abstract

Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1(+)c-KIT(+)) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT(+)). Our data display dynamic transcriptional networks and identify a stem/progenitor gene expression pattern that is characterized by cell adhesion and immune response components including kallikrein-related proteases. We identify 498 expressed lncRNAs, which are potential regulators of multipotency or lineage commitment. By integrating these transcriptome with... (More)

Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1(+)c-KIT(+)) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT(+)). Our data display dynamic transcriptional networks and identify a stem/progenitor gene expression pattern that is characterized by cell adhesion and immune response components including kallikrein-related proteases. We identify 498 expressed lncRNAs, which are potential regulators of multipotency or lineage commitment. By integrating these transcriptome with our recently reported proteome data, we found evidence for posttranscriptional regulation of processes including metabolism and response to oxidative stress. Finally, our study identifies a high number of genes with transcript isoform regulation upon lineage commitment. This in-depth molecular analysis outlines the enormous complexity of expressed coding and noncoding RNAs and posttranscriptional regulation during the early differentiation steps of hematopoietic stem cells toward the myeloid lineage.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Animals, Cell Adhesion, Cell Cycle, Cell Differentiation, Cell Lineage, Energy Metabolism, Female, Flow Cytometry, Gene Expression Profiling, Gene Ontology, Gene Regulatory Networks, Hematopoietic Stem Cells, Immunity, Mice, Inbred C57BL, Multipotent Stem Cells, Myeloid Cells, Proteome, RNA, Long Noncoding, Reverse Transcriptase Polymerase Chain Reaction
in
Stem Cell Reports
volume
3
issue
5
pages
18 pages
publisher
Cell Press
external identifiers
  • Scopus:84922539408
ISSN
2213-6711
DOI
10.1016/j.stemcr.2014.08.012
language
English
LU publication?
no
id
88270b25-04a5-4ed0-8e11-cd9e804612a7
date added to LUP
2016-04-19 10:18:33
date last changed
2016-10-13 05:06:37
@misc{88270b25-04a5-4ed0-8e11-cd9e804612a7,
  abstract     = {<p>Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1(+)c-KIT(+)) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT(+)). Our data display dynamic transcriptional networks and identify a stem/progenitor gene expression pattern that is characterized by cell adhesion and immune response components including kallikrein-related proteases. We identify 498 expressed lncRNAs, which are potential regulators of multipotency or lineage commitment. By integrating these transcriptome with our recently reported proteome data, we found evidence for posttranscriptional regulation of processes including metabolism and response to oxidative stress. Finally, our study identifies a high number of genes with transcript isoform regulation upon lineage commitment. This in-depth molecular analysis outlines the enormous complexity of expressed coding and noncoding RNAs and posttranscriptional regulation during the early differentiation steps of hematopoietic stem cells toward the myeloid lineage.</p>},
  author       = {Klimmeck, Daniel and Cabezas-Wallscheid, Nina and Reyes, Alejandro and von Paleske, Lisa and Renders, Simon and Hansson, Jenny and Krijgsveld, Jeroen and Huber, Wolfgang and Trumpp, Andreas},
  issn         = {2213-6711},
  keyword      = {Animals,Cell Adhesion,Cell Cycle,Cell Differentiation,Cell Lineage,Energy Metabolism,Female,Flow Cytometry,Gene Expression Profiling,Gene Ontology,Gene Regulatory Networks,Hematopoietic Stem Cells,Immunity,Mice, Inbred C57BL,Multipotent Stem Cells,Myeloid Cells,Proteome,RNA, Long Noncoding,Reverse Transcriptase Polymerase Chain Reaction},
  language     = {eng},
  month        = {11},
  number       = {5},
  pages        = {75--858},
  publisher    = {ARRAY(0xb43b9a0)},
  series       = {Stem Cell Reports},
  title        = {Transcriptome-wide profiling and posttranscriptional analysis of hematopoietic stem/progenitor cell differentiation toward myeloid commitment},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2014.08.012},
  volume       = {3},
  year         = {2014},
}