Endothelial and Leptin Receptor Cells Promote the Maintenance of Stem Cells and Hematopoiesis in Early Postnatal Murine Bone Marrow

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2023 Mar 3

PMID 36868235

Authors

Nergis Kara

Yuanyuan Xue

Zhiyu Zhao

Malea M Murphy

Stefano Comazzetto

Ashley Lesser

Liming Du

Sean J Morrison

Affiliations

Soon will be listed here.

Abstract

Mammalian hematopoietic stem cells (HSCs) colonize the bone marrow during late fetal development, and this becomes the major site of hematopoiesis after birth. However, little is known about the early postnatal bone marrow niche. We performed single-cell RNA sequencing of mouse bone marrow stromal cells at 4 days, 14 days, and 8 weeks after birth. Leptin-receptor-expressing (LepR) stromal cells and endothelial cells increased in frequency during this period and changed their properties. At all postnatal stages, LepR cells and endothelial cells expressed the highest stem cell factor (Scf) levels in the bone marrow. LepR cells expressed the highest Cxcl12 levels. In early postnatal bone marrow, SCF from LepR/Prx1 stromal cells promoted myeloid and erythroid progenitor maintenance, while SCF from endothelial cells promoted HSC maintenance. Membrane-bound SCF in endothelial cells contributed to HSC maintenance. LepR cells and endothelial cells are thus important niche components in early postnatal bone marrow.

Citing Articles

Disruption of the moonlighting function of CTF18 in a patient with T-lymphopenia.

Sertori R, Truong B, Singh M, Shinton S, Price R, Sharo A Front Immunol. 2025; 16:1539848.

PMID: 40028343 PMC: 11868726. DOI: 10.3389/fimmu.2025.1539848.

HSPG2 could promote normal haematopoiesis in acute myeloid leukaemia patients after complete remission by repairing bone marrow endothelial progenitor cells.

Li C, Wang Z, Xing T, Shen M, Zhang X, Chen D Clin Transl Med. 2025; 15(2):e70220.

PMID: 39914998 PMC: 11802241. DOI: 10.1002/ctm2.70220.

Cellular crosstalk in the bone marrow niche.

Huang Z, Iqbal Z, Zhao Z, Liu J, Alabsi A, Shabbir M J Transl Med. 2024; 22(1):1096.

PMID: 39627858 PMC: 11613879. DOI: 10.1186/s12967-024-05900-6.

Endothelial heterogeneity in bone marrow: insights across development, adult life and leukemia.

Boueya I, Sandhow L, Albuquerque J, Znaidi R, Passaro D Leukemia. 2024; 39(1):8-24.

PMID: 39528790 PMC: 11717709. DOI: 10.1038/s41375-024-02453-x.

Unlocking the regenerative key: Targeting stem cell factors for bone renewal.

Karima G, Kim H J Tissue Eng. 2024; 15:20417314241287491.

PMID: 39479284 PMC: 11523181. DOI: 10.1177/20417314241287491.

References

Mendez-Ferrer S, Michurina T, Ferraro F, Mazloom A, MacArthur B, Lira S . Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308):829-34. PMC: 3146551. DOI: 10.1038/nature09262. View

Stanley E, Chitu V . CSF-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol. 2014; 6(6). PMC: 4031967. DOI: 10.1101/cshperspect.a021857. View

Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D . Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013; 502(7473):637-43. PMC: 3821873. DOI: 10.1038/nature12612. View

Liu H, Du T, Li C, Yang G . STAT3 phosphorylation in central leptin resistance. Nutr Metab (Lond). 2021; 18(1):39. PMC: 8045279. DOI: 10.1186/s12986-021-00569-w. View

Zhu X, Bergles D, Nishiyama A . NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development. 2007; 135(1):145-57. DOI: 10.1242/dev.004895. View

Comazzetto S, Murphy M, Berto S, Jeffery E, Zhao Z, Morrison S . Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow. Cell Stem Cell. 2019; 24(3):477-486.e6. PMC: 6813769. DOI: 10.1016/j.stem.2018.11.022. View

Shu H, Liu Y, Tang X, Zhang X, Zhou B, Zou W . Tracing the skeletal progenitor transition during postnatal bone formation. Cell Stem Cell. 2021; 28(12):2122-2136.e3. DOI: 10.1016/j.stem.2021.08.010. View

DeFalco J, Tomishima M, Liu H, Zhao C, Cai X, Marth J . Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science. 2001; 291(5513):2608-13. DOI: 10.1126/science.1056602. View

Christodoulou C, Spencer J, Yeh S, Turcotte R, Kokkaliaris K, Panero R . Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020; 578(7794):278-283. PMC: 7021587. DOI: 10.1038/s41586-020-1971-z. View

10.

Oguro H, Ding L, Morrison S . SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell. 2013; 13(1):102-16. PMC: 3736853. DOI: 10.1016/j.stem.2013.05.014. View

11.

Ding L, Saunders T, Enikolopov G, Morrison S . Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012; 481(7382):457-62. PMC: 3270376. DOI: 10.1038/nature10783. View

12.

Kissa K, Herbomel P . Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature. 2010; 464(7285):112-5. DOI: 10.1038/nature08761. View

13.

Zhou B, Ding L, Morrison S . Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1. Elife. 2015; 4:e05521. PMC: 4411515. DOI: 10.7554/eLife.05521. View

14.

Meacham C, Jeffery E, Burgess R, Sivakumar C, Arora M, Stanley A . Adiponectin receptors sustain haematopoietic stem cells throughout adulthood by protecting them from inflammation. Nat Cell Biol. 2022; 24(5):697-707. PMC: 9107511. DOI: 10.1038/s41556-022-00909-9. View

15.

Balordi F, Fishell G . Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci. 2007; 27(22):5936-47. PMC: 6672245. DOI: 10.1523/JNEUROSCI.1040-07.2007. View

16.

Chen J, Miyanishi M, Wang S, Yamazaki S, Sinha R, Kao K . Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature. 2016; 530(7589):223-7. PMC: 4854608. DOI: 10.1038/nature16943. View

17.

Luster A, Unkeless J, Ravetch J . Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985; 315(6021):672-6. DOI: 10.1038/315672a0. View

18.

Himburg H, Termini C, Schlussel L, Kan J, Li M, Zhao L . Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration. Cell Stem Cell. 2018; 23(3):370-381.e5. PMC: 6482945. DOI: 10.1016/j.stem.2018.07.003. View

19.

Flanagan J, Chan D, Leder P . Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell. 1991; 64(5):1025-35. DOI: 10.1016/0092-8674(91)90326-t. View

20.

Ono N, Ono W, Mizoguchi T, Nagasawa T, Frenette P, Kronenberg H . Vasculature-associated cells expressing nestin in developing bones encompass early cells in the osteoblast and endothelial lineage. Dev Cell. 2014; 29(3):330-9. PMC: 4083679. DOI: 10.1016/j.devcel.2014.03.014. View