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Wojtowicz, Edyta E., Mistry, Jayna J., Uzun, Vladimir, Hellmich, Charlotte, Scoones, Anita, Chin, Desmond W., Kettyle, Laura M., Grasso, Francesca, Lord, Allegra M., Wright, David J., Etherington, Graham J., Woll, Petter S., Belderbos, Mirjam E., Bowles, Kristian M. 
ORCID: https://orcid.org/0000-0003-1334-4526, Nerlov, Claus, Haerty, Wilfried ORCID: https://orcid.org/0000-0003-0111-191X, Bystrykh, Leonid V., Jacobsen, Sten Eirik W., Rushworth, Stuart A. and Macaulay, Iain C.
(2023)
Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion.
Genome Biology, 24.
ISSN 1474-760X
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Abstract
Background: Platelets and erythrocytes constitute over 95% of all hematopoietic stem cell output. However, the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Results: We use lentiviral genetic labeling of mouse hematopoietic stem cells to quantify output from all lineages, nucleate, and anucleate, simultaneously linking these with stem and progenitor cell transcriptomic phenotypes using single-cell RNA-sequencing. We observe dynamic shifts of clonal behaviors through time in same-animal peripheral blood and demonstrate that acute platelet depletion shifts the output of multipotent hematopoietic stem cells to the exclusive production of platelets. Additionally, we observe the emergence of new myeloid-biased clones, which support short- and long-term production of blood cells. Conclusions: Our approach enables kinetic studies of multi-lineage output in the peripheral blood and transcriptional heterogeneity of individual hematopoietic stem cells. Our results give a unique insight into hematopoietic stem cell reactivation upon platelet depletion and of clonal dynamics in both steady state and under stress.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: EEW is supported by a Sir Henry Welcome Postdoctoral Fellowship (213731/Z/18/Z), by an Earlham Institute BBSRC Flexible Talent Mobility Fellowship (BB/R50659X/1), and previously by the Swedish Childhood Cancer Foundation Postdoctoral Fellowship (TJ2017-0039) at Karolinska Institutet, Sweden. Work at EI was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through the Core Capability Grant BB/CCG1720/1, BS/E/T/000PR9818 (ICM, WH, GE, VU), and at the Earlham Institute (ICM, WH, GE, VU, DJW) and BBS/E/T/000PR9816 (ICM, GE). AS was supported by the BBSRC-funded Norwich Research Park Biosciences Doctoral Training Partnership grant BB/M011216/1. ICM is additionally supported by BBSRC New Investigator Grant BB/P022073/1. WH was additionally supported by a UK Medical Research Council [MR/P026028/1] award. Next-generation sequencing was delivered via the BBSRC National Capability in Genomics and Single Cell Analysis (BBS/E/T/000PR9816). SAR is supported by the MRC project (MR/T02934X/1). JM was supported by BigC Cancer Charity. CH is funded by Wellcome Trust Clinical Research Fellowship (220534/Z/20/Z). AML was funded by the Swedish Childhood Cancer Foundation (TJ2016-0064). This work was supported by the Swedish Research Council (538–2013-8995 to S.E.W.J.) and The UK Medical Research Council (MC_UU_12009/5 to S.E.W.J., MC_UU_12009/7 to C.N.). |
| Uncontrolled Keywords: | clonal switching,hematopoiesis,lineage tracing,platelet depletion,platelets,ecology, evolution, behavior and systematics,genetics,cell biology ,/dk/atira/pure/subjectarea/asjc/1100/1105 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences Faculty of Science > School of Pharmacy |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Patient Care Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 21 Mar 2024 16:30 |
| Last Modified: | 09 May 2024 10:31 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/94737 |
| DOI: | 10.1186/s13059-023-02976-z |
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