Leptin receptor, a surface marker for a subset of highly engrafting long-term functional hematopoietic stem cells

Abstract

LIST OF ABBREVIATIONS AGM Aorta-genital ridge-mesonephros ALL Acute lymphoblastic leukemia AML Acute myeloid leukemia ANGPT1 Angiopoietin 1 BCSC Breast cancer stem cell BFU-E Burst-forming unit-erythroid BM Bone marrow CB Cord blood CFU Colony-forming unit CFU-GEMM CFU-granulocyte, erythrocyte, macrophage, megakaryocyte CFU-GM CFU-granulocyte,macrophage CH Clonal hematopoiesis CHIP Clonal hematopoiesis of indeterminate potential CLP Common lymphoid progenitor CMP Common myeloid progenitor CPT1 Carnitinepalmitoyl transferase 1 CRU Competitive repopulating unit CSC Cancer stem cell DPP4 Dipeptidyl peptidase 4 E Embryonic EC Endothelial cell EIF Eukaryotic translation initiation factor in type 2 diabetes • Techniques: qRT-PCR.

Age-related decline in LEPR+ hematopoietic stem cell function

“…Consistent with our previous report, proportions of young LEPR-expressing long-term SLAM HSCs (Lin -Sca1 + c-Kit + Flt3 -CD150 + CD48 -) (LSK Flt3 -CD150 + CD48 -, hereafter denoted as SLAM-HSC LT ) and short-term SLAM-HSCs (LSK Flt3 -CD150 -CD48or SLAM-HSC ST ) were significantly lower than LEPRcounterparts (Fig. 1A, B) [2,5]. However, LEPR + SLAM-HSC LT exist at a higher proportion in aged mice as compared to young mice (Fig.…”

“…1F) as well as absolute number of CRUs (Fig. 1G, H, S2D) [2]. Compared to young LEPR + LSK, middle-aged LEPR + LSK cells showed significantly lower donor chimerism and lower number of CRUs.…”

“…However, HSCs are a heterogenous group of cells, and the question remains whether HSC subsets are differentially affected by aging. Our previous work demonstrated in young mice that leptin receptor (LEPR) + HSCs, a highly engrafting subpopulation of HSCs expressing the truncated, non-functional isoform of LEPR under steady-state, exhibit transcriptomic programs enriched for type I interferon (IFN) and interferon-gamma (IFN-γ) associated pathways compared to LEPR -HSCs [2]. Beyond its role in embryonic HSC development, it is known that chronic IFN-γ signaling leads to HSC cycling and ultimately exhaustion [3].…”

Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis

“…It is noteworthy that the significance of this association was abrogated after adjusting for amount of fat in abdomen or thigh. Leptin signaling has been shown to play a significant role in myelopoiesis, lymphopoiesis, and HSC function in mice [54][55][56]. In humans, low leptin levels have been found in HIV lipodystrophy syndrome [45].…”

Sex-specific niche signaling contributes to sexual dimorphism following stem cell transplantation

“…Recovery of the B, T, and macrophage populations in the spleens of M➔M vs. F➔F mice was dramatically different, with M➔M mice displaying higher numbers of B-cells particularly at D21 (5.2M/spleen vs. 3M) and D28 (3.9M/spleen vs. 2.1M), and macrophages at each timepoint, particularly the D21 (3.8M/spleen vs. 1.8M) and D28 ( 3.2M/spleen vs. 1.7M) ( Figure 5C ). RNA sequencing results also demonstrate splenic sex differences between genes associated with hematopoietic regeneration including downregulation of Cfh (potentially reducing splenic inflammation and autoimmunity 29 ), Ptprd ( inhibition of Ptp has been demonstrated to promote regeneration 30 ), Cxcl12 ( suggesting enhanced HSC mobilization ), Epas1(also observed in the BM, which may promote regeneration ), Lepr (which marks long-term HSCs 31 ), and Malat1 (which is downregulated upon hematopoietic differentiation 32 ) in male compared to female recipients ( Figure 5D).…”