Human haematopoietic stem cell lineage commitment is a continuous process

• Verfasst von: Velten, Lars [VerfasserIn]
• Verfasst von: Raffel, Simon [VerfasserIn]
• Verfasst von: Lutz, Christoph [VerfasserIn]
• Verfasst von: Buß, Eike Christian [VerfasserIn]
• Verfasst von: Nowak, Daniel [VerfasserIn]
• Verfasst von: Boch, Tobias [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Trumpp, Andreas [VerfasserIn]
• Verfasst von: Essers, Marieke [VerfasserIn]
• Titel: Human haematopoietic stem cell lineage commitment is a continuous process
• Verf.angabe: Lars Velten, Simon F. Haas, Simon Raffel, Sandra Blaszkiewicz, Saiful Islam, Bianca P. Hennig, Christoph Hirche, Christoph Lutz, Eike C. Buss, Daniel Nowak, Tobias Boch, Wolf-Karsten Hofmann, Anthony D. Ho, Wolfgang Huber, Andreas Trumpp, Marieke A. G. Essers, Lars M. Steinmetz
• E-Jahr: 2017
• Jahr: 20 March 2017
• Umfang: 11 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 25.09.2018
• Titel Quelle: Enthalten in: Nature cell biology
• Ort Quelle: New York, NY : Nature America, 1999
• Jahr Quelle: 2017
• Band/Heft Quelle: 19(2017), 4, Seite 271-281
• ISSN Quelle: 1476-4679
• DOI: doi:10.1038/ncb3493
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581264135

Abstract

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.