library_construction_protocol: In brief, intact bone marrows from mice at the age of 2 months or 22-24 months were flushed from mouse femora and tibiae. Bone marrow cells by pipetting with 1 mL syringe, and then underwent red blood cell lysis using 0.16 M ammonium chloride solution. Low input RNA-seq was performed according to published single-cell RNA-seq protocols with modifications (Tang et al., 2010). Briefly, FACS-sorted 1000 Lin– Scal1+ c-Kit+ CD48– CD150+ (HSC) (2-3 µL) of each sample were transferred into 25 μL cell lysis buffer prepared as follows: 0.9x PCR buffer II, 1.35 mM MgCl2, 0.45% NP40, 4.5 mM DTT, 0.36 U μL–1 RNase inhibitor (ThermoFisher, EN0581), 12.5 nM UP1 primer, 0.045 mM dNTP), following reverse transcription with RT mix prepared as follows: 14.4 U μL–1 Superscript III reverse transcriptase (Invitrogen, 18080-044), 0.48U μL–1 RNase inhibitor, 0.07 U μL–1 T4 gene 32 protein (NEB, #M0300L). cDNA purified with AMPure XP beads (Beckman Coulter, A63881) were used to perform poly A tailing, then one round of PCR enrichment with 13 cycles of amplification was performed. Enriched cDNA was quantified using Qubit dsDNA HS Assay Kit after purification. TruePrepTM DNA library Prep Kit V2 (Vazyme, TD503) was used to prepare RNA seq library following the manufacturer's protocol. Libraries were sequenced as pair-end 150 bp using HiSeq X10. Three technical replicates were included for each type.