Identification and characterization of <i>in vitro</i> expanded hematopoietic stem cells

Liley, James; Bode, Daniel; Kuciński, Iwo; Cull, Alyssa; Bain, Fiona; Becker, H.; Jassinskaja, Maria; Barile, Melania; Boyd, Grace; Belmonte, Miriam; Zeng, Andy G.X.; Igarashi, Kyomi J.; Rubio‐Lara, Juan; Shepherd, Mairi; Clay, Anna; Dick, John E.; Wilkinson, Adam C.; Nakauchi, Hiromitsu; Yamazaki, Satoshi; Göttgens, Berthold; Kent, David G.

doi:10.15252/embr.202255502

Cited by 29 publications

(29 citation statements)

References 82 publications

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“…( 2), unrealistic small estimated values of may be possible because the very small returns a fraction of P-P differentiation as some magnitude. In fact, our group showed that, when the fraction of CD201 + CD150 + KSL population was even around 10%, the post-transplantation chimerism in peripheral blood became almost 0 21 , implying P-P divisions are still possible at least for 10% of the fraction and supporting our assumption on usage of the discretized beta function. 1.…”

Section: Discussionsupporting

confidence: 74%

“…Endothelial Protein C Receptor (EPCR, also known as CD201) exclusively enriches functional HSCs quanti ed by ex vivo and in vivo reconstitution assays 20,21 . We performed single-cell expansion by sorting CD34 −/low CD150 + c-Kit + Sca-1 + lineage marker negative (CD34 − CD150 + KSL) cell populations that are highly enriched in functional HSCs 22,23,24 from mice (Fig.…”

Section: Age-related Bimodal Changes In Functional Hsc Proportionsmentioning

confidence: 99%

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Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Kawahigashi

Iwanami

Takahashi

et al. 2022

Preprint

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Haematopoietic stem cells (HSCs) are somatic stem cells that continuously generate lifelong supply of blood cells through a balance of symmetric and asymmetric divisions. Recently, it is well established that the HSC pool increases with age. However, not much is known about the underlying cause for these observed changes. Here, using a novel method combining single-cell ex vivo HSC expansion with mathematical modeling, we quantify HSC division types (stem cell - stem cell (S-S) division, stem cell - progenitor cell (S-P) division, and progenitor cell - progenitor cell (P-P) division) as a function of the ageing process. Our time-series experiments reveal how changes in these three modes of division can explain the increase in HSC numbers with age. Contrary to the popular notion that HSCs divide predominantly through S-P divisions, we show that S-S divisions are predominant throughout the lifespan of the animal, thereby expanding the HSC pool. We, therefore, provide a novel mathematical model-based experimental validation for reflecting HSC dynamics in vivo.

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Section: Discussionsupporting

confidence: 74%

Section: Age-related Bimodal Changes In Functional Hsc Proportionsmentioning

confidence: 99%

Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Kawahigashi

Iwanami

Takahashi

et al. 2022

Preprint

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“…Cultured HSCs cannot be identified by the same panel of surface markers as freshly isolated HSCs. Endothelial Protein C Receptor (EPCR, also known as CD201) exclusively enriches for functional HSCs, as quantified by e x vivo and in vivo reconstitution assays [ 20 , 26 , 27 ]. The marker, with CD150, has also been recently shown to enrich for cells that possess long-term expansion potential and retain a transcriptional phenotype associated with HSCs after PVA-based culture.…”

Section: Resultsmentioning

confidence: 99%

Age-related changes in the hematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions

Kawahigashi,

Iwanami,

Takahashi

et al. 2024

PLoS ONE

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Hematopoietic stem cells (HSCs) are somatic stem cells that continuously generate lifelong supply of blood cells through a balance of symmetric and asymmetric divisions. It is well established that the HSC pool increases with age. However, not much is known about the underlying cause for these observed changes. Here, using a novel method combining single-cell ex vivo HSC expansion with mathematical modeling, we quantify HSC division types (stem cell—stem cell (S-S) division, stem cell—progenitor cell (S-P) division, and progenitor cell—progenitor cell (P-P) division) as a function of the aging process. Our time-series experiments reveal how changes in these three modes of division can explain the increase in HSC numbers with age. Contrary to the popular notion that HSCs divide predominantly through S-P divisions, we show that S-S divisions are predominant throughout the lifespan of the animal, thereby expanding the HSC pool. We, therefore, provide a novel mathematical model-based experimental validation for reflecting HSC dynamics in vivo.

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“…Although is it known that long-term hematopoietic reconstitution is possible from CD150-cells in the E14.5 FL (Kent et al, 2009; Kim et al, 2006; Papathanasiou et al, 2009), how much of the LT-RU biomass they represent is not known. This is an important issue that requires resolution because of how ubiquitously CD150 expression is used as a hurdle criterion for the quantitative and qualitative analysis of the fetal LT-RU pool (for examples see (Che et al, 2022; Ganuza et al, 2022; Gao et al, 2022; Hall et al, 2022; Lee et al, 2022; Patel et al, 2022; Sakai et al, 2022; Van Deren et al, 2022; Young et al, 2021)).…”

Section: Introductionmentioning

confidence: 99%

Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed

Stonehouse,

Biben,

Weber

et al. 2024

Preprint

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It has been proposed that adult haematopoiesis is sustained by multipotent progenitor (MPP) clones that are specified during development. From an immunophenotypic perspective, it is known that hematopoietic stem cell (HSC) and MPPs are present in the fetal liver yet our understanding of how fetal MPPs functionally compare to those in the adult bone marrow is incomplete. Using acute-term transplantations, we found that at a population-level fetal immunophenotypic MPP classes exhibited similar lineage biases as adult cells, albeit with some difference in lymphoid output. Clonal assessment of fetal MPPs engraftment revealed that lineage biases largely resulted from differences in the pattern of single- or bi-lineage differentiation. Immunophenotypic long-term (LT)- and short-term (ST)-HSCs in the fetal liver were distinguished from MPPs according to propensity for clonal multi-lineage differentiation. We also discovered that a large cohort of long-term repopulating units (LT-RU) were within the immunophenotypic ST-HSC population, a significant portion of these were labelled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will systematically underestimate the size and diversity of the fetal LT-RU pool; and, (2), given fetal LT-RUs with a ST-HSC immunophenotype have the functional attributes required to persist into adulthood.

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Identification and characterization of in vitro expanded hematopoietic stem cells

Abstract: This is a repository copy of Identification and characterization of in vitro expanded hematopoietic stem cells.

Cited by 29 publications

References 82 publications

Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Age-related changes in the haematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

Age-related changes in the hematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions

Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed

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