The hematopoietic landscape at single-cell resolution reveals unexpected stem cell features in naked mole-rats

Abstract

HIGHLIGHTS  Flow cytometry labelling panel to purify viable naked mole-rat HSPCs  The spleen as the major site of erythropoiesis in the naked mole-rat  Naked mole-rats show extrathymic T-cell development under homeostatic conditions  Naked mole-rat hematopoietic stem cells (HSCs) have high OXPHOS activity

Ectopic cervical thymi and no thymic involution until midlife in naked mole-rats

“…Neoteny refers to retention of juvenile phenotypes in adult organisms, hence considering humans neotenic apes (Bufill et al, 2011). NMRs feature an array of neotenic traits (Skulachev et al, 2017), including aspects of their hematopoietic system (Emmrich et al, 2019). Here we found developmental FOXN1 and age-associated AIRE mRNA levels with little to no changes between neonate and 11 year-old adult animals.…”

“…CD4 + /CTLA4 + /CD25 + regulatory T cells (Treg) comprised ~4% in NMR thymus and ~11% in lymph nodes (Figure S3H), compared to 1% of human PB-WBCs or 3% of mouse lymph node cells (Greer et al, 2019), an adaptation in line with an expanded CD4-compartment across all hematopoietic tissues (Emmrich et al, 2019).…”

“…Commitment towards the γδTC lineage is instructed by T cell receptor (TCR) signal strength, whereby PTCRA indicates weak and TCRγδ strong signals at the DN1 stage (Munoz-Ruiz et al, 2017). We found the constant region of the TCRγ chain (TRGC2) marking marrow ETPs (Emmrich et al, 2019), hence the most primitive thymic partition across mouse and naked mole-rat showed conserved TRGC2 overexpression (Figure 3a). Mature murine γδTCs are enriched for TRGC2.…”

“…The copyright holder for this preprint this version posted August 2, 2021. ; https://doi.org/10.1101/2021.08.01.454657 doi: bioRxiv preprint (Emmrich et al, 2019).…”

Immune competence and spleen size scale with colony status in the naked mole-rat

“…NES, normalized enrichment score; pval, p value; padj, adjusted p value. Significantly enriched pathways using NM-R cell type signatures from Hilton and colleagues (“H”) and Emmrich and colleagues (“E”) [16, 43] and established hallmark pathways (“HM”). GC: granulocytes.…”