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

dc.contributor.authorMorcos, Mina N. F.
dc.contributor.authorLi, Congxin
dc.contributor.authorMunz, Clara M.
dc.contributor.authorGreco, Alessandro
dc.contributor.authorDressel, Nicole
dc.contributor.authorReinhardt, Susanne
dc.contributor.authorSameith, Katrin
dc.contributor.authorDahl, Andreas
dc.contributor.authorBecker, Nils B.
dc.contributor.authorRoers, Axel
dc.contributor.authorHöfer, Thomas
dc.contributor.authorGerbaulet, Alexander
dc.date.accessioned2025-04-09T15:49:51Z
dc.date.issued2022
dc.date.updated2024-11-24T07:47:38Z
dc.description.abstractHematopoietic 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.en
dc.description.sponsorshipProjekt DEAL
dc.identifier.issn2041-1723
dc.identifier.other1926333322
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-161760de
dc.identifier.urihttps://elib.uni-stuttgart.de/handle/11682/16176
dc.identifier.urihttps://doi.org/10.18419/opus-16157
dc.language.isoen
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/764698
dc.relation.uridoi:10.1038/s41467-022-31914-z
dc.rightsCC BY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570
dc.subject.ddc620
dc.titleFate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesisen
dc.typearticle
dc.type.versionpublishedVersion
ubs.fakultaetEnergie-, Verfahrens- und Biotechnik
ubs.fakultaetFakultätsübergreifend / Sonstige Einrichtung
ubs.institutInstitut für Biomedizinische Genetik
ubs.institutFakultätsübergreifend / Sonstige Einrichtung
ubs.publikation.seiten13
ubs.publikation.sourceNature communications 13 (2022), No. 4504
ubs.publikation.typZeitschriftenartikel

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