Competition Between Hematopoietic Stem and Progenitor Cells Controls Hematopoietic Stem Cell Compartment Size

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 8

PMID 35941168

Authors

Runfeng Miao

Harim Chun

Xing Feng

Ana Cordeiro Gomes

Jungmin Choi

Joao P Pereira

Affiliations

Soon will be listed here.

Abstract

Cellular competition for limiting hematopoietic factors is a physiologically regulated but poorly understood process. Here, we studied this phenomenon by hampering hematopoietic progenitor access to Leptin receptor mesenchymal stem/progenitor cells (MSPCs) and endothelial cells (ECs). We show that HSC numbers increase by 2-fold when multipotent and lineage-restricted progenitors fail to respond to CXCL12 produced by MSPCs and ECs. HSCs are qualitatively normal, and HSC expansion only occurs when early hematopoietic progenitors but not differentiated hematopoietic cells lack CXCR4. Furthermore, the MSPC and EC transcriptomic heterogeneity is stable, suggesting that it is impervious to major changes in hematopoietic progenitor interactions. Instead, HSC expansion correlates with increased availability of membrane-bound stem cell factor (mSCF) on MSPCs and ECs presumably due to reduced consumption by cKit-expressing hematopoietic progenitors. These studies suggest that an intricate homeostatic balance between HSCs and proximal hematopoietic progenitors is regulated by cell competition for limited amounts of mSCF.

Citing Articles

Competitive signaling and cellular communications in myocardial infarction response.

Nair V, Demitri C, Thankam F Mol Biol Rep. 2025; 52(1):129.

PMID: 39820809 PMC: 11739196. DOI: 10.1007/s11033-025-10236-5.

CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.

Rondeau V, Kalogeraki M, Roland L, Nader Z, Gourhand V, Bonaud A Sci Signal. 2024; 17(860):eadl5100.

PMID: 39471249 PMC: 11733996. DOI: 10.1126/scisignal.adl5100.

Engraftment of human mesenchymal stem cells in a severely immunodeficient mouse.

Kato Y, Ohno Y, Ito R, Taketani T, Matsuzaki Y, Miyagi S Inflamm Regen. 2024; 44(1):40.

PMID: 39327616 PMC: 11426203. DOI: 10.1186/s41232-024-00353-2.

Bone marrow niches for hematopoietic stem cells.

Pereira A, Galli S, Nombela-Arrieta C Hemasphere. 2024; 8(8):e133.

PMID: 39086665 PMC: 11289431. DOI: 10.1002/hem3.133.

Stromal STAT5-Mediated Trophic Activity Regulates Hematopoietic Niche Factors.

Wang Z, Emmel G, Lim H, Zhu W, Kosters A, Ghosn E Stem Cells. 2023; 41(10):944-957.

PMID: 37465968 PMC: 11009694. DOI: 10.1093/stmcls/sxad055.

References

Liu Y, Zhang S, Chen Y, Shi K, Zou B, Liu J . ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells. Stem Cell Reports. 2018; 11(1):258-273. PMC: 6117479. DOI: 10.1016/j.stemcr.2018.05.016. View

Upadhaya S, Krichevsky O, Akhmetzyanova I, Sawai C, Fooksman D, Reizis B . Intravital Imaging Reveals Motility of Adult Hematopoietic Stem Cells in the Bone Marrow Niche. Cell Stem Cell. 2020; 27(2):336-345.e4. PMC: 7415613. DOI: 10.1016/j.stem.2020.06.003. View

Zehentmeier S, Pereira J . Cell circuits and niches controlling B cell development. Immunol Rev. 2019; 289(1):142-157. PMC: 6464388. DOI: 10.1111/imr.12749. View

Xu C, Gao X, Wei Q, Nakahara F, Zimmerman S, Mar J . Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow. Nat Commun. 2018; 9(1):2449. PMC: 6015052. DOI: 10.1038/s41467-018-04726-3. View

Hafemeister C, Satija R . Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 2019; 20(1):296. PMC: 6927181. DOI: 10.1186/s13059-019-1874-1. View

Chung Y, Park B, Kang Y, Kim T, Eaves C, Oh I . Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration. Blood. 2006; 108(4):1208-15. DOI: 10.1182/blood-2006-01-010199. 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

Hirata Y, Furuhashi K, Ishii H, Li H, Pinho S, Ding L . CD150 Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine. Cell Stem Cell. 2018; 22(3):445-453.e5. PMC: 6534147. DOI: 10.1016/j.stem.2018.01.017. View

Ogawa M, Matsuzaki Y, Hayashi S, Kunisada T, Sudo T, Kina T . Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med. 1991; 174(1):63-71. PMC: 2118893. DOI: 10.1084/jem.174.1.63. View

10.

Linnekin D . Early signaling pathways activated by c-Kit in hematopoietic cells. Int J Biochem Cell Biol. 1999; 31(10):1053-74. DOI: 10.1016/s1357-2725(99)00078-3. View

11.

Miao R, Lim V, Kothapalli N, Ma Y, Fossati J, Zehentmeier S . Hematopoietic Stem Cell Niches and Signals Controlling Immune Cell Development and Maintenance of Immunological Memory. Front Immunol. 2020; 11:600127. PMC: 7726109. DOI: 10.3389/fimmu.2020.600127. View

12.

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

13.

Pertea M, Kim D, Pertea G, Leek J, Salzberg S . Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016; 11(9):1650-67. PMC: 5032908. DOI: 10.1038/nprot.2016.095. View

14.

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

15.

Beck T, Gomes A, Cyster J, Pereira J . CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. J Exp Med. 2014; 211(13):2567-81. PMC: 4267240. DOI: 10.1084/jem.20140457. View

16.

Sawai C, Babovic S, Upadhaya S, Knapp D, Lavin Y, Lau C . Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals. Immunity. 2016; 45(3):597-609. PMC: 5054720. DOI: 10.1016/j.immuni.2016.08.007. View

17.

Tzeng Y, Li H, Kang Y, Chen W, Cheng W, Lai D . Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. Blood. 2010; 117(2):429-39. DOI: 10.1182/blood-2010-01-266833. View

18.

Bruns I, Lucas D, Pinho S, Ahmed J, Lambert M, Kunisaki Y . Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med. 2014; 20(11):1315-20. PMC: 4258871. DOI: 10.1038/nm.3707. View

19.

Tikhonova A, Dolgalev I, Hu H, Sivaraj K, Hoxha E, Cuesta-Dominguez A . The bone marrow microenvironment at single-cell resolution. Nature. 2019; 569(7755):222-228. PMC: 6607432. DOI: 10.1038/s41586-019-1104-8. View

20.

Silberstein L, Goncalves K, Kharchenko P, Turcotte R, Kfoury Y, Mercier F . Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators. Cell Stem Cell. 2016; 19(4):530-543. PMC: 5402355. DOI: 10.1016/j.stem.2016.07.004. View