Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis

Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We fin...

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Published in:Nature communications 2022-08, Vol.13 (1), p.4504-4504, Article 4504
Main Authors: Morcos, Mina N. F., Li, Congxin, Munz, Clara M., Greco, Alessandro, Dressel, Nicole, Reinhardt, Susanne, Sameith, Katrin, Dahl, Andreas, Becker, Nils B., Roers, Axel, Höfer, Thomas, Gerbaulet, Alexander
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13/100
13/31
38/39
38/91
631/114/2397
631/136/232/2051/1339
631/532/1542
631/532/2118/1542
64/60
Cell fate
Computer applications
Fate maps
Gene sequencing
Hematopoiesis
Hematopoietic stem cells
Humanities and Social Sciences
Lymphocytes
Mapping
Megakaryocytes
multidisciplinary
Myelopoiesis
Physiology
Progenitor cells
Science
Science (multidisciplinary)
Stem cells
Thrombopoiesis
Thrombopoietin
Tracking
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description Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48 hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48 −/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis. Hematopoietic stem cells produce diverse cell lineages. Here, the authors apply single-cell RNA-seq, computational integration of non-perturbative approaches for fate-mapping, and mitotic tracking to chart lineage decisions in native hematopoiesis and identify megakaryocyte progenitors that directly link HSCs to megakaryocytes.
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subjects 13/100
13/31
38/39
38/91
631/114/2397
631/136/232/2051/1339
631/532/1542
631/532/2118/1542
64/60
Cell fate
Computer applications
Fate maps
Gene sequencing
Hematopoiesis
Hematopoietic stem cells
Humanities and Social Sciences
Lymphocytes
Mapping
Megakaryocytes
multidisciplinary
Myelopoiesis
Physiology
Progenitor cells
Science
Science (multidisciplinary)
Stem cells
Thrombopoiesis
Thrombopoietin
Tracking
title Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis
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