biostudies-literatureUnknown5(20)Weiss ACIHRBone marrow (BM) is the primary site of hematopoiesis and is responsible for a lifelong supply of all blood cell lineages. The process of hematopoiesis follows key intrinsic programs that also integrate instructive signals from the BM niche. First identified as an erythropoietin-potentiating factor, the tissue inhibitor of metalloproteinase (TIMP) protein family has expanded to 4 members and has widely come to be viewed as a classical regulator of tissue homeostasis. By virtue of metalloprotease inhibition, TIMPs not only regulate extracellular matrix turnover but also control growth factor bioavailability. The 4 mammalian TIMPs possess overlapping enzyme-inhibition profiles and have never been studied for their cumulative role in hematopoiesis. Here, we show that TIMPs are critical for poBlood advances3960-3974https://www.ebi.ac.uk/biostudies/studies/S-EPMC8945646biostudies-literatureAbnormal B-cell development in TIMP-deficient bone marrow.PMC8945646Narala SFang HSaw SShetty RAiken AWeiss AWaterhouse PDKhokha RShao YWAliar KfalseAbnormal B-cell development in TIMP-deficient bone marrow.Bone marrow (BM) is the primary site of hematopoiesis and is responsible for a lifelong supply of all blood cell lineages. The process of hematopoiesis follows key intrinsic programs that also integrate instructive signals from the BM niche. First identified as an erythropoietin-potentiating factor, the tissue inhibitor of metalloproteinase (TIMP) protein family has expanded to 4 members and has widely come to be viewed as a classical regulator of tissue homeostasis. By virtue of metalloprotease inhibition, TIMPs not only regulate extracellular matrix turnover but also control growth factor bioavailability. The 4 mammalian TIMPs possess overlapping enzyme-inhibition profiles and have never been studied for their cumulative role in hematopoiesis. Here, we show that TIMPs are critical for po2021-01-01T00:00:00Z2021 Oct2026-03-27T16:43:13.243Z2025-04-07T11:41:39.694ZS-EPMC89456463450045710.1182/bloodadvances.2020004101