論文 - 詳細
| RRC ID | 68919 |
|---|---|
| 著者 | Georgolopoulos G, Psatha N, Iwata M, Nishida A, Som T, Yiangou M, Stamatoyannopoulos JA, Vierstra J. |
| タイトル | Discrete regulatory modules instruct hematopoietic lineage commitment and differentiation. |
| ジャーナル | Nat Commun |
| Abstract |
Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. Here we perform dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide insights into the temporally regulated synergy of the cis- and the trans-regulatory components underlying hematopoietic lineage commitment and differentiation. |
| 巻・号 | 12(1) |
| ページ | 6790 |
| 公開日 | 2021-11-23 |
| DOI | 10.1038/s41467-021-27159-x |
| PII | 10.1038/s41467-021-27159-x |
| PMID | 34815405 |
| PMC | PMC8611072 |
| MeSH | Cell Line Cell Lineage / genetics* Chromatin / genetics* Chromatin / metabolism Colony-Forming Units Assay Deoxyribonuclease I / metabolism Gene Expression Regulation, Developmental* Hematopoiesis / genetics* Hematopoietic Stem Cells / physiology* Humans Leukocytes, Mononuclear Primary Cell Culture Promoter Regions, Genetic RNA-Seq Single-Cell Analysis Transcription Factors / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |