Sex-specific bone marrow populations regulate skeletal phenotype and identify CD74-marked osteoclast precursor subsets

Female bone marrow transplanted into male hosts increases vertebral trabecular and cortical bone mass in 8-week-old lethally irradiated mice, highlighting cell-intrinsic sex effects on skeletal phenotype.

• Why it matters: Sex-linked differences in bone accrual and maintenance are known hormonally, but the bone marrow cell-intrinsic factors that mediate these disparities remain unclear.
• What they did: Male or female bone marrow was transplanted into male hosts, followed by Micro-CT and comparative single-cell sequencing to identify CD11B+CD74+ myeloid clusters; X-linked Tlr7 and Kdm6a marked a CD11B+CD74+ population.
• The result: Male donor chimeras had higher proportions of Cd74-expressing clusters and more bone marrow-resident CD11B+CD74+ cells under physiological conditions, while female CD11B+CD74+ cells showed diminished osteoclastogenesis.

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