Single-Cell RNA Sequencing of Haematopoietic Progenitor Heterogeneity in Human Bone Marrow

Abstract

Background: Human haematopoietic progenitors were long mapped as discrete marker-defined compartments. Single-cell
RNA sequencing has replaced that tree with a continuous transcriptional landscape.
Objective: To assess how securely the continuum interpretation holds against technical artefact.
Methods: Narrative review of index-sorted and droplet single-cell studies, reference atlases and clonal-tracing work.
Findings: Index-sorted profiling of 1,413 cells from two donors showed a continuum rather than discrete oligopotent stages,
and clonal marks independent of expression agreed. Atlases detect only 525 to 880 genes per cell, while ambient RNA at 2 to
6% and multiplets at 1.6 to 3.1% push data toward apparent continuity.
Conclusions: A continuous progenitor landscape is supported; finer substructure within it is not, since noise of comparable
magnitude can generate it