The evolving composition of the BM niche for HSCs from embryonic development to advanced aging. (A) Graphical overview of the cellular and molecular 3-dimensional organization of the HSC niche (upper panel) as well as the HSC distance distribution from putative BM niche populations across life span (lower panel; embryonic: 1; early postnatal: 2; adult: 3; aging: 4). Corresponding factors are in capital letters when protein data are available or in small letters for transcriptomic data. Arrows indicate increase or decrease in expression compared with the adult stage. Topographic maps illustrate the distance distribution of HSCs from putative BM niche populations, with dark green contour areas marking the distance bin where most HSCs are located (lower panel). An example of the expected distance distribution for BM populations being close (proximal) or far away (distal) from HSCs is shown (lower left panel). Transparent topographic maps marked with a question mark represent HSC-niche associations that remain unknown. (B) Graphical representation of dynamic changes in the cellular composition and relative frequency of key BM populations across life span. The thickness of the displayed 2-dimensional shape corresponds to the relative frequency of the respective population per age group. Some populations are frequent at the embryo stage but decrease during adulthood (osteo-chondrocyte progenitors and embryonic MSCs), whereas others increase in adulthood or during aging. A gray shape has been added for Schwann cells to demonstrate contradictory findings. Angpt1, angiopoietin 1; Csf1, colony-stimulating factor 1; Cxcl12, C-X-C motif chemokine ligand 12; CCL5, C-C motif chemokine ligand 5; Dll4, delta like ligand 4; IGF1, insulin-like growth factor 1; Jag1, jagged-1; OPN, osteopontin; PTN, pleiotrophin; ROS, reactive oxygen species; Scf, stem cell factor.