A Single-cell Resolved Cell-cell Communication Model Explains Lineage Commitment in Hematopoiesis

Overview

Journal Development

Specialty Biology

Date 2021 Dec 22

PMID 34935903

Citations 5

Authors

Megan K Rommelfanger

Adam L MacLean

Affiliations

Soon will be listed here.

Abstract

Cells do not make fate decisions independently. Arguably, every cell-fate decision occurs in response to environmental signals. In many cases, cell-cell communication alters the dynamics of the internal gene regulatory network of a cell to initiate cell-fate transitions, yet models rarely take this into account. Here, we have developed a multiscale perspective to study the granulocyte-monocyte versus megakaryocyte-erythrocyte fate decisions. This transition is dictated by the GATA1-PU.1 network: a classical example of a bistable cell-fate system. We show that, for a wide range of cell communication topologies, even subtle changes in signaling can have pronounced effects on cell-fate decisions. We go on to show how cell-cell coupling through signaling can spontaneously break the symmetry of a homogenous cell population. Noise, both intrinsic and extrinsic, shapes the decision landscape profoundly, and affects the transcriptional dynamics underlying this important hematopoietic cell-fate decision-making system. This article has an associated 'The people behind the papers' interview.

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References

Kamenz J, Gelens L, Ferrell Jr J . Bistable, Biphasic Regulation of PP2A-B55 Accounts for the Dynamics of Mitotic Substrate Phosphorylation. Curr Biol. 2020; 31(4):794-808.e6. PMC: 7904671. DOI: 10.1016/j.cub.2020.11.058. View

Muller E, Grinenko T, Pompe T, Waskow C, Werner C . Space constraints govern fate of hematopoietic stem and progenitor cells in vitro. Biomaterials. 2015; 53:709-15. DOI: 10.1016/j.biomaterials.2015.02.095. View

Craciun G, Tang Y, Feinberg M . Understanding bistability in complex enzyme-driven reaction networks. Proc Natl Acad Sci U S A. 2006; 103(23):8697-702. PMC: 1592242. DOI: 10.1073/pnas.0602767103. View

Alon U . Network motifs: theory and experimental approaches. Nat Rev Genet. 2007; 8(6):450-61. DOI: 10.1038/nrg2102. View

Handly L, Pilko A, Wollman R . Paracrine communication maximizes cellular response fidelity in wound signaling. Elife. 2015; 4:e09652. PMC: 4686426. DOI: 10.7554/eLife.09652. View

Wang J, Tu C, Zhang H, Huo Y, Menu E, Liu J . Single-cell analysis at the protein level delineates intracellular signaling dynamic during hematopoiesis. BMC Biol. 2021; 19(1):201. PMC: 8428103. DOI: 10.1186/s12915-021-01138-6. View

Iber D, Menshykau D . The control of branching morphogenesis. Open Biol. 2013; 3(9):130088. PMC: 3787747. DOI: 10.1098/rsob.130088. View

Zarubin T, Han J . Activation and signaling of the p38 MAP kinase pathway. Cell Res. 2005; 15(1):11-8. DOI: 10.1038/sj.cr.7290257. View

Lo Celso C, Scadden D . The haematopoietic stem cell niche at a glance. J Cell Sci. 2011; 124(Pt 21):3529-35. PMC: 3215569. DOI: 10.1242/jcs.074112. View

10.

Thurley K, Wu L, Altschuler S . Modeling Cell-to-Cell Communication Networks Using Response-Time Distributions. Cell Syst. 2018; 6(3):355-367.e5. PMC: 5913757. DOI: 10.1016/j.cels.2018.01.016. View

11.

Herault A, Binnewies M, Leong S, Calero-Nieto F, Zhang S, Kang Y . Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis. Nature. 2017; 544(7648):53-58. PMC: 5383507. DOI: 10.1038/nature21693. View

12.

Tyson J, Chen K, Novak B . Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol. 2003; 15(2):221-31. DOI: 10.1016/s0955-0674(03)00017-6. View

13.

Ferrell Jr J . Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol. 2002; 14(2):140-8. DOI: 10.1016/s0955-0674(02)00314-9. View

14.

Shea M, Ackers G . The OR control system of bacteriophage lambda. A physical-chemical model for gene regulation. J Mol Biol. 1985; 181(2):211-30. DOI: 10.1016/0022-2836(85)90086-5. View

15.

Brewer C, Chu E, Chin M, Lu R . Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells. Cell Rep. 2016; 15(8):1848-57. PMC: 4880538. DOI: 10.1016/j.celrep.2016.04.061. View

16.

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

17.

Huang S, Guo Y, May G, Enver T . Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev Biol. 2007; 305(2):695-713. DOI: 10.1016/j.ydbio.2007.02.036. View

18.

Moor A, Itzkovitz S . Spatial transcriptomics: paving the way for tissue-level systems biology. Curr Opin Biotechnol. 2017; 46:126-133. DOI: 10.1016/j.copbio.2017.02.004. View

19.

Duff C, Smith-Miles K, Lopes L, Tian T . Mathematical modelling of stem cell differentiation: the PU.1-GATA-1 interaction. J Math Biol. 2011; 64(3):449-68. DOI: 10.1007/s00285-011-0419-3. View

20.

Giladi A, Cohen M, Medaglia C, Baran Y, Li B, Zada M . Dissecting cellular crosstalk by sequencing physically interacting cells. Nat Biotechnol. 2020; 38(5):629-637. DOI: 10.1038/s41587-020-0442-2. View