Why are cell populations maintained via multiple compartments?

Feliciangeli, Flavia; Dreiwi, Hanan; López-García, Martín; Castro Ponce, Mario; Molina-París, Carmen; Lythe, Grant

doi:10.1098/rsif.2022.0629

Title: Why are cell populations maintained via multiple compartments?

Journal Article · Wed Nov 09 00:00:00 UTC 2022 · Interface (Online)

DOI: https://doi.org/10.1098/rsif.2022.0629 · OSTI ID:2470453

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University of Leeds (United Kingdom); Bayer AG, Leverkusen (Germany)
University of Leeds (United Kingdom)
Universidad Pontificia Comillas, Madrid (Spain)
University of Leeds (United Kingdom); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

We consider the maintenance of ‘product’ cell populations from ‘progenitor’ cells via a sequence of one or more cell types, or compartments, where each cell’s fate is chosen stochastically. If there is only one compartment then large amplification, that is, a large ratio of product cells to progenitors comes with disadvantages. The product cell population is dominated by large families (cells descended from the same progenitor) and many generations separate, on average, product cells from progenitors. These disadvantages are avoided using suitably constructed sequences of compartments: the amplification factor of a sequence is the product of the amplification factors of each compartment, while the average number of generations is a sum over contributions from each compartment. Passing through multiple compartments is, in fact, an efficient way to maintain a product cell population from a small flux of progenitors, avoiding excessive clonality and minimizing the number of rounds of division en route. We use division, exit and death rates, estimated from measurements of single-positive thymocytes, to choose illustrative parameter values in the single-compartment case. We also consider a five-compartment model of thymocyte differentiation, from double-negative precursors to single-positive product cells.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: European Commission; MCIN/AEI/10.13039/501100011033; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 2470453

Report Number(s):: LA-UR--21-2563

Journal Information:: Interface (Online), Journal Name: Interface (Online) Journal Issue: 196 Vol. 19; ISSN 1742-5662

Publisher:: The Royal SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (84)

Branching Processes in Biology Kimmel, Marek; Axelrod, David E. Interdisciplinary Applied Mathematics https://doi.org/10.1007/b97371	book	January 2002
Sample path properties of the average generation of a Bellman–Harris process Meli, Gianfelice; Weber, Tom S.; Duffy, Ken R. Journal of Mathematical Biology, Vol. 79, Issue 2 https://doi.org/10.1007/s00285-019-01373-0	journal	May 2019
A short proof of Darboux's lemma Knuth, Donald E.; Wilf, Herbert S. Applied Mathematics Letters, Vol. 2, Issue 2 https://doi.org/10.1016/0893-9659(89)90007-4	journal	January 1989
How many Cell-Generations ? Kay, H. . E. M. The Lancet, Vol. 286, Issue 7409 https://doi.org/10.1016/S0140-6736(65)90763-4	journal	August 1965
Computationally Efficient Bounds for the Catalan Numbers Dutton, Ronald D.; Brigham, Robert C. European Journal of Combinatorics, Vol. 7, Issue 3 https://doi.org/10.1016/S0195-6698(86)80024-5	journal	July 1986
Determining Lineage Pathways from Cellular Barcoding Experiments Perié, Leïla; Hodgkin, Philip D.; Naik, Shalin H. Cell Reports, Vol. 6, Issue 4 https://doi.org/10.1016/j.celrep.2014.01.016	journal	February 2014
Stem cell self-renewal in regeneration and cancer: Insights from mathematical modeling Stiehl, Thomas; Marciniak-Czochra, Anna Current Opinion in Systems Biology, Vol. 5 https://doi.org/10.1016/j.coisb.2017.09.006	journal	October 2017
Stem-cell dynamics and lineage topology from in vivo fate mapping in the hematopoietic system Höfer, Thomas; Barile, Melania; Flossdorf, Michael Current Opinion in Biotechnology, Vol. 39 https://doi.org/10.1016/j.copbio.2016.04.001	journal	June 2016
Maintenance of Peripheral Naive T Cells Is Sustained by Thymus Output in Mice but Not Humans den Braber, Ineke; Mugwagwa, Tendai; Vrisekoop, Nienke Immunity, Vol. 36, Issue 2 https://doi.org/10.1016/j.immuni.2012.02.006	journal	February 2012
Continuous Effector CD8 + T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population Chu, H. Hamlet; Chan, Shiao-Wei; Gosling, John Paul Immunity, Vol. 45, Issue 1 https://doi.org/10.1016/j.immuni.2016.06.013	journal	July 2016
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals Sawai, Catherine M.; Babovic, Sonja; Upadhaya, Samik Immunity, Vol. 45, Issue 3 https://doi.org/10.1016/j.immuni.2016.08.007	journal	September 2016
T Cell Development by the Numbers Krueger, Andreas; Ziętara, Natalia; Łyszkiewicz, Marcin Trends in Immunology, Vol. 38, Issue 2 https://doi.org/10.1016/j.it.2016.10.007	journal	February 2017
Hematopoiesis in numbers Cosgrove, Jason; Hustin, Lucie S. P.; de Boer, Rob J. Trends in Immunology, Vol. 42, Issue 12 https://doi.org/10.1016/j.it.2021.10.006	journal	December 2021
A mathematical model of hematopoiesis—I. Periodic chronic myelogenous leukemia Colijn, Caroline; Mackey, Michael C. Journal of Theoretical Biology, Vol. 237, Issue 2 https://doi.org/10.1016/j.jtbi.2005.03.033	journal	November 2005
How many TCR clonotypes does a body maintain? Lythe, Grant; Callard, Robin E.; Hoare, Rollo L. Journal of Theoretical Biology, Vol. 389 https://doi.org/10.1016/j.jtbi.2015.10.016	journal	January 2016
Stem cell homeostasis by integral feedback through the niche Becker, Nils B.; Günther, Matthias; Li, Congxin Journal of Theoretical Biology, Vol. 481 https://doi.org/10.1016/j.jtbi.2018.12.029	journal	November 2019
A new mechanism shapes the naïve CD8 + T cell repertoire: the selection for full diversity Gonçalves, Pedro; Ferrarini, Marco; Molina-Paris, Carmen Molecular Immunology, Vol. 85 https://doi.org/10.1016/j.molimm.2017.01.026	journal	May 2017
The variance of the average depth of a pure birth process converges to 7 Duffy, Ken R.; Meli, Gianfelice; Shneer, Seva Statistics & Probability Letters, Vol. 150 https://doi.org/10.1016/j.spl.2019.02.015	journal	July 2019
Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies Bowman, Robert L.; Busque, Lambert; Levine, Ross L. Cell Stem Cell, Vol. 22, Issue 2 https://doi.org/10.1016/j.stem.2018.01.011	journal	February 2018
Intracellular competition for fates in the immune system Duffy, Ken R.; Hodgkin, Philip D. Trends in Cell Biology, Vol. 22, Issue 9 https://doi.org/10.1016/j.tcb.2012.05.004	journal	September 2012
Stem cells, cancer, and cancer stem cells Reya, Tannishtha; Morrison, Sean J.; Clarke, Michael F. Nature, Vol. 414, Issue 6859 https://doi.org/10.1038/35102167	journal	November 2001
Cell senescence and cancer Mathon, Nicole F.; Lloyd, Alison C. Nature Reviews Cancer, Vol. 1, Issue 3 https://doi.org/10.1038/35106045	journal	December 2001
Dynamics of chronic myeloid leukaemia Michor, Franziska; Hughes, Timothy P.; Iwasa, Yoh Nature, Vol. 435, Issue 7046 https://doi.org/10.1038/nature03669	journal	June 2005
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo Busch, Katrin; Klapproth, Kay; Barile, Melania Nature, Vol. 518, Issue 7540 https://doi.org/10.1038/nature14242	journal	February 2015
T-cell stimuli independently sum to regulate an inherited clonal division fate Marchingo, J. M.; Prevedello, G.; Kan, A. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms13540	journal	November 2016
Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations Derényi, Imre; Szöllősi, Gergely J. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14545	journal	February 2017
CD8+ T cell diversification by asymmetric cell division Flossdorf, Michael; Rössler, Jens; Buchholz, Veit R. Nature Immunology, Vol. 16, Issue 9 https://doi.org/10.1038/ni.3235	journal	August 2015
Evidence from the generation of immunoglobulin G–secreting cells that stochastic mechanisms regulate lymphocyte differentiation Hasbold, Jhagvaral; Corcoran, Lynn M.; Tarlinton, David M. Nature Immunology, Vol. 5, Issue 1 https://doi.org/10.1038/ni1016	journal	November 2003
Evidence that hematopoiesis may be a stochastic process in vivo Abkowitz, Janis L.; Catlin, Sandra N.; Guttorp, Peter Nature Medicine, Vol. 2, Issue 2 https://doi.org/10.1038/nm0296-190	journal	February 1996
Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications Roeder, Ingo; Horn, Matthias; Glauche, Ingmar Nature Medicine, Vol. 12, Issue 10 https://doi.org/10.1038/nm1487	journal	October 2006
Mechanisms of aging: public or private? Partridge, Linda; Gems, David Nature Reviews Genetics, Vol. 3, Issue 3 https://doi.org/10.1038/nrg753	journal	March 2002
Sonic hedgehog signalling in T-cell development and activation Crompton, Tessa; Outram, Susan V.; Hager-Theodorides, Ariadne L. Nature Reviews Immunology, Vol. 7, Issue 9 https://doi.org/10.1038/nri2151	journal	August 2007
Determining γδ versus αβ T cell development Ciofani, Maria; Zúñiga-Pflücker, Juan Carlos Nature Reviews Immunology, Vol. 10, Issue 9 https://doi.org/10.1038/nri2820	journal	August 2010
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Akbar, Arne N.; Henson, Sian M. Nature Reviews Immunology, Vol. 11, Issue 4 https://doi.org/10.1038/nri2959	journal	March 2011
Effector and memory T-cell differentiation: implications for vaccine development Kaech, Susan M.; Wherry, E. John; Ahmed, Rafi Nature Reviews Immunology, Vol. 2, Issue 4 https://doi.org/10.1038/nri778	journal	April 2002
CD8+ T cell differentiation and dysfunction in cancer Philip, Mary; Schietinger, Andrea Nature Reviews Immunology, Vol. 22, Issue 4 https://doi.org/10.1038/s41577-021-00574-3	journal	July 2021
Replicative history marks transcriptional and functional disparity in the CD8+ T cell memory pool Bresser, Kaspar; Kok, Lianne; Swain, Arpit C. Nature Immunology, Vol. 23, Issue 5 https://doi.org/10.1038/s41590-022-01171-9	journal	April 2022
The distribution of cellular turnover in the human body Sender, Ron; Milo, Ron Nature Medicine, Vol. 27, Issue 1 https://doi.org/10.1038/s41591-020-01182-9	journal	January 2021
Reporting T cell proliferation Mukhopadhyay, Madhura Nature Methods, Vol. 19, Issue 5 https://doi.org/10.1038/s41592-022-01505-3	journal	May 2022
Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer Johnston, M. D.; Edwards, C. M.; Bodmer, W. F. Proceedings of the National Academy of Sciences, Vol. 104, Issue 10 https://doi.org/10.1073/pnas.0611179104	journal	February 2007
Murine thymic selection quantified using a unique method to capture deleted T cells Stritesky, G. L.; Xing, Y.; Erickson, J. R. Proceedings of the National Academy of Sciences, Vol. 110, Issue 12 https://doi.org/10.1073/pnas.1217532110	journal	March 2013
Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system Sinclair, C.; Bains, I.; Yates, A. J. Proceedings of the National Academy of Sciences, Vol. 110, Issue 31 https://doi.org/10.1073/pnas.1304859110	journal	July 2013
Fluctuating fitness shapes the clone-size distribution of immune repertoires Desponds, Jonathan; Mora, Thierry; Walczak, Aleksandra M. Proceedings of the National Academy of Sciences, Vol. 113, Issue 2 https://doi.org/10.1073/pnas.1512977112	journal	December 2015
Temporal fate mapping reveals age-linked heterogeneity in naive T lymphocytes in mice Hogan, Thea; Gossel, Graeme; Yates, Andrew J. Proceedings of the National Academy of Sciences, Vol. 112, Issue 50 https://doi.org/10.1073/pnas.1517246112	journal	November 2015
A compartment size-dependent selective threshold limits mutation accumulation in hierarchical tissues Grajzel, Dániel; Derényi, Imre; Szöllősi, Gergely J. Proceedings of the National Academy of Sciences, Vol. 117, Issue 3 https://doi.org/10.1073/pnas.1913104117	journal	January 2020
A Stochastic Model of stem cell Proliferation, Based on the Growth of Spleen Colony-Forming Cells Till, J. E.; McCulloch, E. A.; Siminovitch, L. Proceedings of the National Academy of Sciences, Vol. 51, Issue 1 https://doi.org/10.1073/pnas.51.1.29	journal	January 1964
An Elementary Evaluation of the Catalan Numbers Singmaster, David The American Mathematical Monthly, Vol. 85, Issue 5 https://doi.org/10.1080/00029890.1978.11994597	journal	May 1978
Asymmetric cell division during T cell development controls downstream fate Pham, Kim; Shimoni, Raz; Charnley, Mirren Journal of Cell Biology, Vol. 210, Issue 6 https://doi.org/10.1083/jcb.201502053	journal	September 2015
Thymocytes may persist and differentiate without any input from bone marrow progenitors Peaudecerf, Laetitia; Lemos, Sara; Galgano, Alessia Journal of Experimental Medicine, Vol. 209, Issue 8 https://doi.org/10.1084/jem.20120845	journal	July 2012
Thymus-autonomous T cell development in the absence of progenitor import Martins, Vera C.; Ruggiero, Eliana; Schlenner, Susan M. Journal of Experimental Medicine, Vol. 209, Issue 8 https://doi.org/10.1084/jem.20120846	journal	July 2012
Self-renewal of thymocytes in the absence of competitive precursor replenishment Boehm, Thomas Journal of Experimental Medicine, Vol. 209, Issue 8 https://doi.org/10.1084/jem.20121412	journal	July 2012
Exact solution of a two-type branching process: models of tumor progression Antal, Tibor; Krapivsky, P. L. Journal of Statistical Mechanics: Theory and Experiment, Vol. 2011, Issue 08 https://doi.org/10.1088/1742-5468/2011/08/P08018	journal	August 2011
Mutations of Bacteria from Virus Sensitivity to Virus Resistance Luria, S. E.; Delbrück, M. Genetics, Vol. 28, Issue 6 https://doi.org/10.1093/genetics/28.6.491	journal	November 1943
A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues Werner, Benjamin; Dingli, David; Traulsen, Arne Journal of The Royal Society Interface, Vol. 10, Issue 85 https://doi.org/10.1098/rsif.2013.0349	journal	August 2013
Replicative cellular age distributions in compartmentalized tissues Böttcher, Marvin A.; Dingli, David; Werner, Benjamin Journal of The Royal Society Interface, Vol. 15, Issue 145 https://doi.org/10.1098/rsif.2018.0272	journal	August 2018
Competition-Induced Criticality in a Model of Meme Popularity Gleeson, James P.; Ward, Jonathan A.; O’Sullivan, Kevin P. Physical Review Letters, Vol. 112, Issue 4 https://doi.org/10.1103/PhysRevLett.112.048701	journal	January 2014
The natural history of naive T cells from birth to maturity Seddon, Benedict; Yates, Andrew J. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12694	journal	August 2018
Some deterministic and stochastic mathematical models of naïve T-cell homeostasis Lythe, Grant; Molina-París, Carmen Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12696	journal	August 2018
Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses Chang, John T.; Palanivel, Vikram R.; Kinjyo, Ichiko Science, Vol. 315, Issue 5819 https://doi.org/10.1126/science.1139393	journal	March 2007
Heterogeneous Differentiation Patterns of Individual CD8+ T Cells Gerlach, C.; Rohr, J. C.; Perie, L. Science, Vol. 340, Issue 6132 https://doi.org/10.1126/science.1235487	journal	March 2013
Variation in cancer risk among tissues can be explained by the number of stem cell divisions Tomasetti, Cristian; Vogelstein, Bert Science, Vol. 347, Issue 6217 https://doi.org/10.1126/science.1260825	journal	January 2015
Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention Tomasetti, Cristian; Li, Lu; Vogelstein, Bert Science, Vol. 355, Issue 6331 https://doi.org/10.1126/science.aaf9011	journal	March 2017
Modulation of asymmetric cell division as a mechanism to boost CD8 ⁺ T cell memory Borsa, Mariana; Barnstorf, Isabel; Baumann, Nicolas S. Science Immunology, Vol. 4, Issue 34 https://doi.org/10.1126/sciimmunol.aav1730	journal	April 2019
T Cell Fate at the Single-Cell Level Buchholz, Veit R.; Schumacher, Ton N. M.; Busch, Dirk H. Annual Review of Immunology, Vol. 34, Issue 1 https://doi.org/10.1146/annurev-immunol-032414-112014	journal	May 2016
A Critique of Compartmental Analysis Zierler, Kenneth Annual Review of Biophysics and Bioengineering, Vol. 10, Issue 1 https://doi.org/10.1146/annurev.bb.10.060181.002531	journal	June 1981
Hematopoiesis and its disorders: a systems biology approach Whichard, Zakary L.; Sarkar, Casim A.; Kimmel, Marek Blood, Vol. 115, Issue 12 https://doi.org/10.1182/blood-2009-08-215798	journal	March 2010
To portray clonal evolution in blood cancer, count your stem cells Lyne, Anne-Marie; Laplane, Lucie; Perié, Leïla Blood, Vol. 137, Issue 14 https://doi.org/10.1182/blood.2020008407	journal	April 2021
Differentiation and proliferation of hematopoietic stem cells Ogawa, M. Blood, Vol. 81, Issue 11 https://doi.org/10.1182/blood.V81.11.2844.2844	journal	June 1993
In vivo kinetics of murine hemopoietic stem cells Abkowitz, Janis L.; Golinelli, Daniela; Harrison, David E. Blood, Vol. 96, Issue 10 https://doi.org/10.1182/blood.V96.10.3399	journal	November 2000
Visualizing hematopoiesis as a stochastic process Xu, Jason; Wang, Yiwen; Guttorp, Peter Blood Advances, Vol. 2, Issue 20 https://doi.org/10.1182/bloodadvances.2018023705	journal	October 2018
generatingfunctionology Wilf, Herbert S. https://doi.org/10.1201/b10576	reference-book	January 2005
Dynamics of Mutant Cells in Hierarchical Organized Tissues Werner, Benjamin; Dingli, David; Lenaerts, Tom PLoS Computational Biology, Vol. 7, Issue 12 https://doi.org/10.1371/journal.pcbi.1002290	journal	December 2011
The Role of Symmetric Stem Cell Divisions in Tissue Homeostasis Yang, Jienian; Plikus, Maksim V.; Komarova, Natalia L. PLOS Computational Biology, Vol. 11, Issue 12 https://doi.org/10.1371/journal.pcbi.1004629	journal	December 2015
The invasion of de-differentiating cancer cells into hierarchical tissues Zhou, Da; Luo, Yue; Dingli, David PLOS Computational Biology, Vol. 15, Issue 7 https://doi.org/10.1371/journal.pcbi.1007167	journal	July 2019
Symmetric vs. Asymmetric Stem Cell Divisions: An Adaptation against Cancer? Shahriyari, Leili; Komarova, Natalia L. PLoS ONE, Vol. 8, Issue 10 https://doi.org/10.1371/journal.pone.0076195	journal	October 2013
Distribution of the branching-process population among generations Samuels, M. L. Journal of Applied Probability, Vol. 8, Issue 4 https://doi.org/10.2307/3212230	journal	December 1971
Theories and Quantification of Thymic Selection Yates, Andrew J. Frontiers in Immunology, Vol. 5 https://doi.org/10.3389/fimmu.2014.00013	journal	January 2014
From pre-DP, post-DP, SP4, and SP8 Thymocyte Cell Counts to a Dynamical Model of Cortical and Medullary Selection Sawicka, Maria; Stritesky, Gretta L.; Reynolds, Joseph Frontiers in Immunology, Vol. 5 https://doi.org/10.3389/fimmu.2014.00019	journal	January 2014
Modeling the Dynamics of T-Cell Development in the Thymus Robert, Philippe A.; Kunze-Schumacher, Heike; Greiff, Victor Entropy, Vol. 23, Issue 4 https://doi.org/10.3390/e23040437	journal	April 2021
Comprehensive Assessment and Mathematical Modeling of T Cell Population Dynamics and Homeostasis Thomas-Vaslin, Véronique; Altes, Hester Korthals; de Boer, Rob J. The Journal of Immunology, Vol. 180, Issue 4 https://doi.org/10.4049/jimmunol.180.4.2240	journal	February 2008
T Cell Acute Lymphoblastic Leukemia as a Consequence of Thymus Autonomy Ballesteros-Arias, Luna; Silva, Joana G.; Paiva, Rafael A. The Journal of Immunology, Vol. 202, Issue 4 https://doi.org/10.4049/jimmunol.1801373	journal	February 2019
Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions Werner, Benjamin; Beier, Fabian; Hummel, Sebastian eLife, Vol. 4 https://doi.org/10.7554/eLife.08687	journal	October 2015
The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes de Greef, Peter C.; Oakes, Theres; Gerritsen, Bram eLife, Vol. 9 https://doi.org/10.7554/eLife.49900	journal	March 2020
HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity Tak, Tamar; Prevedello, Giulio; Simon, Gaël eLife, Vol. 10 https://doi.org/10.7554/eLife.60624	journal	May 2021

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
biomathematics
branching process
cell fate
clonality
generation
probability generating function
progenitor cell
science & technology

Title: Why are cell populations maintained via multiple compartments?

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