Single-cell RNA-seq technology lends a hand into HSC ontogeny.

Pengxu Qian,Linheng Li

doi:10.1007/s11427-016-5092-8

Abstract

Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the “panjunctional sarcoplasmic reticulum” hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.

Highlights

Hematopoietic stem cells (HSCs) are rare populations in the bone marrow of adult mammals which produce millions of blood cells for daily circulation by balancing self-renewal and multi-lineage differentiation
The second wave, termed definitive hematopoiesis, gives rise to HSCs with long-term reconstitution capability that arise from hemogenic endothelium (HE) in the aorta-gonad mesonephros (AGM) region, as well as the placental labyrinth and vitelline and umbilical arteries, and subsequently colonize the fetal liver (FL), spleen, thymus, and eventually occupy the bone marrow (Orkin and Zon, 2008)
Zhou F et al made great efforts by performing multiple experiments, including single-cell co-culture/transplantation assays and single-cell RNA sequencing (RNA-seq), in five cell types related to HSC ontogeny, endothelial cells (ECs), T1 pre-HSCs, T2 CD41low HSCs, E12 and E14 FL HSCs

Summary

Introduction

Hematopoietic stem cells (HSCs) are rare populations in the bone marrow of adult mammals which produce millions of blood cells for daily circulation by balancing self-renewal and multi-lineage differentiation.

Results

Conclusion