| Autor: |
Ewa Sitnicka, David Bryder, Göran Karlsson, Fatemeh Safi, Ram Krishna Thakur, Sarah Warsi, Charlotta Böiers, Parashar Dhapola, Eva Erlandsson |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
SUMMARYThe 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 investigated single-cell chromatin accessibility of Lineage−, cKit+, 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 revealed a population of LSK FMS-like tyrosine kinase 3(Flt3)intCD9highcells 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, 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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