RT Journal Article
SR Electronic
T1 Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.29.069062
DO 10.1101/2020.04.29.069062
A1 Fatemeh Safi
A1 Parashar Dhapola
A1 Sarah Warsi
A1 Eva Erlandsson
A1 Ewa Sitnicka
A1 David Bryder
A1 Charlotta Böiers
A1 Ram Krishna Thakur
A1 Göran Karlsson
YR 2020
UL http://biorxiv.org/content/early/2020/05/01/2020.04.29.069062.abstract
AB 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 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)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, 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.Competing Interest StatementThe authors have declared no competing interest.