Forskningsoutput per år
Forskningsoutput per år
Fatemeh Safi, Parashar Dhapola, Sarah Warsi, Mikael Sommarin, Eva Erlandsson, Jonas Ungerbäck, Rebecca Warfvinge, Ewa Sitnicka, David Bryder, Charlotta Böiers, Ram Krishna Thakur, Göran Karlsson
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor motifs reveals a population of LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures, pointing to a simultaneous gain of both lympho-myeloid and megakaryocyte-erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors and display multi-lineage capacity in vitro and in vivo but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.
Originalspråk | engelska |
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Artikelnummer | 110798 |
Tidskrift | Cell Reports |
Volym | 39 |
Nummer | 6 |
DOI | |
Status | Published - 2022 maj 10 |
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)