Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells

Abstract

Hematopoietic stem cells (HSCs) and distinct multipotent progenitor populations (MPP1-4) contained within the Lin- Sca-1+ c-Kit+ (LSK) compartment have previously been identified using diverse surface marker panels. Here, we phenotypically define and functionally characterize MPP5 (LSK CD34+ CD135- CD48- CD150-). Upon transplantation, MPP5 support initial emergency myelopoiesis followed by stable contribution to the lymphoid lineage. Since MPP5 are capable of generating MPP1-4, but not HSCs, they represent a dynamic and versatile component of the MPP network. To characterize all hematopoietic stem and progenitor cells (HSPCs), we performed RNA-seq analysis to identify specific transcriptomic landscapes of HSCs and MPP1-5. This was complemented by single-cell (sc) RNA-seq analysis of LSK cells to establish the differentiation trajectories from HSCs to MPP1-5. In agreement with the functional reconstitution activity, MPP5 are located immediately downstream of HSCs but upstream of the more committed MPP2-4. This study provides a comprehensive analysis of the LSK compartment, focusing on the functional and molecular characteristics of the newly defined MPP5 subset.

Dntt expression reveals developmental hierarchy and lineage specification of hematopoietic progenitors

“…While different multipotent precursors have been proposed, there is general consensus that only a small fraction of HSCs generates most of the hematopoietic progeny 39 , 40 . In line with this view, we showed that only a minor fraction of HSCs was cycling, and was therefore the likely source of most mature cells, potetially aligning with the recently described CD34 + CD135 − CD48 − CD150 − MPP5 41 .…”

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

“…[ 44 ] Sca‐1 is the other marker of mouse HSCs; Sca‐1‐positive cells can be found in the bone marrow, spleen, and peripheral blood, which also includes some progenitor cells in addition to HSCs. [ 45 ] Zhou et al. [ 46 ] reported that the transplant of Sca‐1‐positive hematopoietic stem/progenitor cells could reconstruct the hematopoietic function of mice suffering from lethal doses of radiation.…”

Massive expansion of multiple clones in the mouse hematopoietic system long after whole-body X-irradiation

“…The mutation frequencies were also determined in hematopoietic colonies derived from sorting single lineage − Sca-1 + c-Kit + CD34 − CD150 + CD48 − long-term hematopoietic stem cells (HSCs) and lineage − Sca-1 + c-Kit + CD34 + multipotent progenitors (MPPs) into 96-well plates (Supplementary Fig. S2 ) 19 , 20 . These cells were allowed to form colonies in MethoCult FG M3434 medium (STEMCELL Technologies, Vancouver, Canada) at 37 °C and 5% CO 2 for 14 days.…”