ArticleBMC biology2015
Mechanisms of blood homeostasis: lineage tracking and a neutral model of cell populations in rhesus macaques.
Article in BMC biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
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- Clonal abundance patterns in hematopoiesis: Mathematical modeling and parameter estimation.Frontiers in systems biology · 2023Article
- Phenomenology and dynamics of competitive ecosystems beyond the niche-neutral regimes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation.Frontiers in immunology · 2021Article
- The clonal repopulation of HSPC gene modified with anti-HIV-1 RNAi is not affected by preexisting HIV-1 infection.Science advances · 2020Article
- Tracing the Dynamics of Stem Cell Fate.Cold Spring Harbor perspectives in biology · 2020Review
- Diversity in biology: definitions, quantification and models.Physical biology · 2020Article
- Stem cell bioengineering: building from stem cell biology.Nature reviews. Genetics · 2018Review
- Modeling large fluctuations of thousands of clones during hematopoiesis: The role of stem cell self-renewal and bursty progenitor dynamics in rhesus macaque.PLoS computational biology · 2018Article
- Single-Cell RNA Sequencing: A New Window into Cell Scale Dynamics.Biophysical journal · 2018Review
- Determining the role of inflammation in the selection of JAK2 mutant cells in myeloproliferative neoplasms.Journal of theoretical biology · 2017Article
- Feedback control in planarian stem cell systems.BMC systems biology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundHow a potentially diverse population of hematopoietic stem cells (HSCs) differentiates and proliferates to supply more than 10(11) mature blood cells every day in humans remains a key biological question. We investigated this process by quantitatively analyzing the clonal structure of peripheral blood that is generated by a population of transplanted lentivirus-marked HSCs in myeloablated rhesus macaques. Each transplanted HSC generates a clonal lineage of cells in the peripheral blood that is then detected and quantified through deep sequencing of the viral vector integration sites (VIS) common within each lineage. This approach allowed us to observe, over a period of 4-12 years, hundreds of distinct clonal lineages.
resultsWhile the distinct clone sizes varied by three orders of magnitude, we found that collectively, they form a steady-state clone size-distribution with a distinctive shape. Steady-state solutions of our model show that the predicted clone size-distribution is sensitive to only two combinations of parameters. By fitting the measured clone size-distributions to our mechanistic model, we estimate both the effective HSC differentiation rate and the number of active HSCs.
conclusionsOur concise mathematical model shows how slow HSC differentiation followed by fast progenitor growth can be responsible for the observed broad clone size-distribution. Although all cells are assumed to be statistically identical, analogous to a neutral theory for the different clone lineages, our mathematical approach captures the intrinsic variability in the times to HSC differentiation after transplantation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.