Human haematopoietic stem cell lineage commitment is a continuous process.
Lars VeltenSimon F HaasSimon RaffelSandra BlaszkiewiczSaiful IslamBianca P HennigChristoph HircheChristoph LutzEike C BussDaniel NowakTobias BochWolf-Karsten HofmannAnthony D HoWolfgang HuberAndreas TrumppMarieke A G EssersLars M SteinmetzPublished in: Nature cell biology (2017)
Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations. Instead, unilineage-restricted cells emerge directly from a 'continuum of low-primed undifferentiated haematopoietic stem and progenitor cells' (CLOUD-HSPCs). Distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of haematopoiesis. These data reveal a continuous landscape of human steady-state haematopoiesis downstream of HSCs and provide a basis for the understanding of haematopoietic malignancies.
Keyphrases
- single cell
- stem cells
- rna seq
- endothelial cells
- gene expression
- high throughput
- induced pluripotent stem cells
- induced apoptosis
- cell therapy
- electronic health record
- dna methylation
- genome wide
- signaling pathway
- cell proliferation
- cell death
- mesenchymal stem cells
- machine learning
- deep learning
- endoplasmic reticulum stress
- network analysis
- artificial intelligence
- pi k akt