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Luteinizing hormone signaling restricts hematopoietic stem cell expansion during puberty
Author(s) -
Peng Yi Jacky,
Yu Hua,
Hao Xiaoxin,
Dong Wenjie,
Yin Xiujuan,
Lin Minghui,
Zheng Junke,
Zhou Bo O
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201898984
Subject(s) - biology , luteinizing hormone , haematopoiesis , stem cell , hormone , stem cell factor , microbiology and biotechnology , signal transduction , hematopoietic stem cell , endocrinology , medicine
The number and self‐renewal capacity of hematopoietic stem cells ( HSC s) are tightly regulated at different developmental stages. Many pathways have been implicated in regulating HSC development in cell autonomous manners; however, it remains unclear how HSC s sense and integrate developmental cues. In this study, we identified an extrinsic mechanism by which HSC number and functions are regulated during mouse puberty. We found that the HSC number in postnatal bone marrow reached homeostasis at 4 weeks after birth. Luteinizing hormone, but not downstream sex hormones, was involved in regulating HSC homeostasis during this period. Expression of luteinizing hormone receptor (Lhcgr) is highly restricted in HSC s and multipotent progenitor cells in the hematopoietic hierarchy. When Lhcgr was deleted, HSC s continued to expand even after 4 weeks after birth, leading to abnormally elevated hematopoiesis and leukocytosis. In a murine acute myeloid leukemia model, leukemia development was significantly accelerated upon Lhcgr deletion. Together, our work reveals an extrinsic counting mechanism that restricts HSC expansion during development and is physiologically important for maintaining normal hematopoiesis and inhibiting leukemogenesis.