The distribution of cellular turnover in the human body

Abstract

We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial cells. In terms of cell numbers, close to 90% of the (0.33 ± 0.02) × 1012 cells per day turnover was blood cells.

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Fig. 1: The turnover rates of cells in the human body.
Fig. 2: The turnover rates of cellular mass in the human body.

Data availability

To generate our estimates of cellular turnover, we extracted values from the literature as detailed in the attached spreadsheet files. Our analysis pipeline consists of about 15 different Jupyter notebooks that use the data extracted from the literature as inputs for generating our estimates. The data extracted for the purpose of our analysis, as well as the results of our analysis are summarized in tables available in the GitHub repository located at https://github.com/milo-lab/cellular_turnover.

Code availability

We provide the code for generating all numeric estimates at https://github.com/milo-lab/cellular_turnover.

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Acknowledgements

We thank Y. Bar-on, Y. Beit-Yannai, J. Brown, Y. Dor, A. Egozi, A. Erez, G. Eshel, S. Fuchs, D. Gluck, L. Greenspoon, D. Hochhauser, S. Itzkovitz, E. Krieger, R. Phillips, R. Scherz-Shouval, L. Shachar, I. Shavitt, L. Shlush, A. Tendler and A. Wides for helpful discussions. This research was supported by the European Research Council (project NOVCARBFIX 646827), Israel Science Foundation (grant 740/16), Beck-Canadian Center for Alternative Energy Research, Dana and Yossie Hollander, Ullmann Family Foundation, Helmsley Charitable Foundation, Larson Charitable Foundation, Wolfson Family Charitable Trust, Charles Rothschild, Selmo Nussenbaum (R.M.), the Israeli Council for Higher Education via the Weizmann Data Science Research Center and by a research grant from Madame Olga Klein – Astrachan (R.S.). R.M. is the Charles and Louise Gartner Professional Chair.

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R.S. and R.M. conceived and performed the study and wrote the manuscript.

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Correspondence to Ron Milo.

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Peer review information Joao Monteiro was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Extended data

Extended Data Fig. 1 Detailed distribution of the cellular turnover rate of human cells by cell type.

To clarify the presentation, Fig. 1 and Fig. 2 in the manuscript body text only refer to the major groups of cells, presenting only the large contributions to the total turnover. This figure gives the same distribution but at a higher resolution, in which groups such as gastrointestinal cells, lymphocytes and lung cells are divided into their subpopulations. Polygon areas represent the fraction of total daily cell replacement for which the cell category accounts. Visualization performed using the online tool at http://bionic-vis.biologie.uni-greifswald.de/.

Extended Data Fig. 2 Detailed distribution of cellular mass turnover rates of human cells by cell type.

Presentation of the cellular mass turnover rates of human cells at higher resolution that in Fig. 2, which describes only the three largest groups of cell types (gastrointestinal cells, lymphocytes, and lung cells) from Fig. 2. are divided into their subpopulation. Polygon areas represent the fraction of total daily cell replacement for which the cell category accounts.

Extended Data Fig. 3 Distribution of lifespan measurements of epithelial cells in the different segments of the gastrointestinal tract (GIT).

For each segment (that is, stomach, small intestine, colon), the mean values and standard deviation from the different sources are presented on the left. The size of the point represents the number of measurements. In the middle, the mean values of each method are presented with error bars denoting 1 standard error. On the right-hand side, the overall mean value is shown with its standard error estimate.

Extended Data Fig. 4 Cellular mass accumulation rate during development.

a. Mean mass of a human male from gestation through 18 years. Data taken from ICRP,2002. Grey line represents the gestation period. Blue line represents the postnatal period. b. Magnification of the early years of development, including gestation. c. The rate of mass accumulation calculated from the derivation of the cellular mass by time (derived from total mass assuming cellular mass represent a constant fraction of two third of total mass). Units were converted to grams per day. The mean cellular mass turnover rate in adult man homeostasis is given as reference. d. The rate of mass accumulation calculated from the derivation of the mass by time normalized to the total mass. The Y-axis is given in logarithmic scale. The mean cellular mass turnover rate in homeostasis as the percentage of the total weight of an adult man is given as reference.

Supplementary information

Supplementary Information

Supplementary Tables 1–4

Reporting Summary

Supplementary Table 5

Cell type numbers and turnover rates database.

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Sender, R., Milo, R. The distribution of cellular turnover in the human body. Nat Med 27, 45–48 (2021). https://doi.org/10.1038/s41591-020-01182-9

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