Hematopoiesis in numbers

Informed by published measurements, our calculations suggest that, in mice, 5 × 103 hematopoietic stem cells (HSCs) can give rise to 1010 hematopoietic cells, while, in humans, 2.5 × 104–1.3 × 106 HSCs can give rise to 1013 mature hematopoietic cells In humans and mice, most hematopoietic cells are short-lived, on the order of days or weeks. As such, blood cells are constantly being produced to maintain blood homeostasis. In humans, blood cells account for 90% of all cellular turnover. Our calculations predict that the amount of murine and human myeloid and erythroid cells produced each day are approximately the same order of magnitude, despite the absolute number of erythroid cells being several orders of magnitude higher than myeloid cells in both species. This is due to large differences in the expected lifespan of each cell type. Despite recent progress, reports on the absolute measurements of cell numbers across tissues throughout lifespans are missing for many cell types and species, particularly in humans; this represents a fruitful area of empirical investigation. Hematopoiesis is a dynamic process in which stem and progenitor cells give rise to the ~1013 blood and immune cells distributed throughout the human body. We argue that a quantitative description of hematopoiesis can help consolidate existing data, identify knowledge gaps, and generate new hypotheses. Here, we review known numbers in murine and, where possible, human hematopoiesis, and consolidate murine numbers into a set of reference values. We present estimates of cell numbers, division and differentiation rates, cell size, and macromolecular composition for each hematopoietic cell type. We also propose guidelines to improve the reporting of measurements and highlight areas in which quantitative data are lacking. Overall, we show how quantitative approaches can be used to understand key properties of hematopoiesis. Hematopoiesis is a dynamic process in which stem and progenitor cells give rise to the ~1013 blood and immune cells distributed throughout the human body. We argue that a quantitative description of hematopoiesis can help consolidate existing data, identify knowledge gaps, and generate new hypotheses. Here, we review known numbers in murine and, where possible, human hematopoiesis, and consolidate murine numbers into a set of reference values. We present estimates of cell numbers, division and differentiation rates, cell size, and macromolecular composition for each hematopoietic cell type. We also propose guidelines to improve the reporting of measurements and highlight areas in which quantitative data are lacking. Overall, we show how quantitative approaches can be used to understand key properties of hematopoiesis. technique to estimate population sizes when it is not possible to count each individual cell. The method involves taking a small population of cells and labeling them, then reintroducing them back into their initial environment and determining the ratio of marked to unmarked cells at a later timepoint. human progenitor compartment containing HSCs, MPPs, and restricted-potential progenitors. give rise to B and T lymphocytes. In mice, they express the following markers: cKitlow Sca1low IL7R+ Flk2–. give rise to erythroid, megakaryocyte, and myeloid lineages. In mice, they express the following markers: cKit+ Sca1– CD16/32– CD34+. stem or progenitor cell that is in the process of changing into a more mature hematopoietic cell type. a dye is split equally between daughter cells during cell division. Consequently, the amount of dye in each cell is indicative of how many times it has divided, over a small number of generations. chromosome replication in the absence of a cell division, resulting in a polypoidal cell. labeling cells with a heritable mark to understand developmental processes. give rise to the myeloid lineages. In mice, they express the following markers: cKit+ Sca1– CD16/32+ CD34+. functionally defined as a multipotent cell capable of long-term self-renewal. In this study, we consider an immunophenotypic HSC to express the following pattern of markers: Lin–Kit+ Sca-1+CD150+CD48–. in gene therapy, a viral vector is used to introduce new genetic material into a host organism. Given that the integration of the virus is stochastic, the precise location of the new genetic material in the host genome acts as a genetic label to perform fate mapping. cell that does not express surface markers associated with the mature blood cell lineages. fate mapping carried out at single cell resolution, typically by introducing a genetic label. express the following markers in mice: Sca1– FcyRlow CD9+ CD41+. give rise to erythroblasts and megakaryocytes. In mice, they expresses the following markers: cKit+ Sca1– CD16/32– CD34–. functionally defined as a cell capable of producing all lineages but lacking long-term self-renewal. In this study, we consider that murine MPPs are all Lin–Kit+ Sca-1+ cells that are not within the immunophenotypic HSC compartment. potential to differentiate into diverse blood cell lineages. formation of new blood cells from stem cells that have been injected into a conditioned (typically irradiated) host. hematopoietic cells that give rise to multiple cell types, but that are incapable of creating all hematopoietic lineages. Therefore, these cells have less potential than MPPs and HSCs; population comprises CMPs, CLPs, GMPs, MEPs, and MkPs. cell division with maintenance of an undifferentiated cell state.