AI Article Synopsis
- Extrinsic and intrinsic regulators maintain tight control of hematopoietic stem cells (HSCs), which develop into various blood cell types.
- The research investigated differentially expressed genes (DEGs) in long-term and short-term HSCs, revealing differences in their stem cell functions despite their close developmental relation.
- A new computational method was established to analyze the relationship between gene expression and regulatory elements, highlighting the role of 24 transcription factors (TFs) that interact with a robust regulatory network to enable HSCs to respond flexibly and quickly to environmental changes.
Article Abstract
Extrinsic and intrinsic regulators are responsible for the tight control of hematopoietic stem cells (HSCs), which differentiate into all blood cell lineages. To understand the fundamental basis of HSC biology, we focused on differentially expressed genes (DEGs) in long-term and short-term HSCs, which are closely related in terms of cell development but substantially differ in their stem cell capacity. To analyze the transcriptional regulation of the DEGs identified in the novel transcriptome profiles obtained by our RNA-seq analysis, we developed a computational method to model the linear relationship between gene expression and the features of putative regulatory elements. The transcriptional regulation modes characterized here suggest the importance of transcription factors (TFs) that are expressed at steady state or at low levels. Remarkably, we found that 24 differentially expressed TFs targeting 21 putative TF-binding sites contributed significantly to transcriptional regulation. These TFs tended to be modulated by other nondifferentially expressed TFs, suggesting that HSCs can achieve flexible and rapid responses via the control of nondifferentially expressed TFs through a highly complex regulatory network. Our novel transcriptome profiles and new method are powerful tools for studying the mechanistic basis of cell fate decisions.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977923 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093853 | PLOS |
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