Spleen stroma maintains progenitors and supports long-term hematopoiesis

Helen C O'Neill, Kristin L Griffiths, Pravin Periasamy, Rebecca A Hinton, Sawang Petvises, Ying-ying Hey, Jonathan K H Tan

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Abstract

Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of stromal niches producing cells of multiple lineages. Limited success has been achieved in the past with induction of hematopoiesis in vitro. Previously, spleen long-term stromal cultures (LTC) were shown to continuously support restricted hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo equivalent dendritic cell type was then described which is specific for spleen. The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like CD11c(lo)CD11b(hi)CD8α-MHC-II- cell which differs phenotypically and functionally from monocytes/macrophages and conventional and plasmacytoid DC. Splenic stroma is now shown to maintain HSPC and to support their restricted in vitro differentiation to give this 'L-DC' subset. In order to characterise progenitors of this distinct cell type, LTC were analysed for cell subsets produced, and these subsets sorted and assessed for hematopoietic potential in subsequent co-cultures over STX3 stroma. Progenitors were defined as a lineage (Lin)(-)ckit(lo) subset reflecting HSPC. Furthermore, when Lin(-)ckit(hi)Sca1(+)Flt3(-) HSPC were sorted from bone marrow, they colonised splenic stroma with long-term production of L-DC. The maintenance of HSPC by splenic stroma was confirmed when non-adherent cells collected from LTC showed oligopotent reconstitution of the hematopoietic compartment of lethally irradiated mice. All data support a model whereby spleen houses a niche for HSPC in the resting state, with production of progenitors, and their differentiation to give tissue-specific antigen presenting cells.

Original languageEnglish
Pages (from-to)354-63
Number of pages10
JournalCurrent Stem Cell Research and Therapy
Volume9
Issue number4
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Hematopoiesis
Hematopoietic Stem Cells
Spleen
Dendritic Cells
Cell Lineage
Antigen-Presenting Cells
Coculture Techniques
Monocytes
Stem Cells
Bone Marrow
Macrophages
Maintenance

Cite this

O'Neill, Helen C ; Griffiths, Kristin L ; Periasamy, Pravin ; Hinton, Rebecca A ; Petvises, Sawang ; Hey, Ying-ying ; Tan, Jonathan K H. / Spleen stroma maintains progenitors and supports long-term hematopoiesis. In: Current Stem Cell Research and Therapy. 2014 ; Vol. 9, No. 4. pp. 354-63.
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abstract = "Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of stromal niches producing cells of multiple lineages. Limited success has been achieved in the past with induction of hematopoiesis in vitro. Previously, spleen long-term stromal cultures (LTC) were shown to continuously support restricted hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo equivalent dendritic cell type was then described which is specific for spleen. The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like CD11c(lo)CD11b(hi)CD8α-MHC-II- cell which differs phenotypically and functionally from monocytes/macrophages and conventional and plasmacytoid DC. Splenic stroma is now shown to maintain HSPC and to support their restricted in vitro differentiation to give this 'L-DC' subset. In order to characterise progenitors of this distinct cell type, LTC were analysed for cell subsets produced, and these subsets sorted and assessed for hematopoietic potential in subsequent co-cultures over STX3 stroma. Progenitors were defined as a lineage (Lin)(-)ckit(lo) subset reflecting HSPC. Furthermore, when Lin(-)ckit(hi)Sca1(+)Flt3(-) HSPC were sorted from bone marrow, they colonised splenic stroma with long-term production of L-DC. The maintenance of HSPC by splenic stroma was confirmed when non-adherent cells collected from LTC showed oligopotent reconstitution of the hematopoietic compartment of lethally irradiated mice. All data support a model whereby spleen houses a niche for HSPC in the resting state, with production of progenitors, and their differentiation to give tissue-specific antigen presenting cells.",
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Spleen stroma maintains progenitors and supports long-term hematopoiesis. / O'Neill, Helen C; Griffiths, Kristin L; Periasamy, Pravin; Hinton, Rebecca A; Petvises, Sawang; Hey, Ying-ying; Tan, Jonathan K H.

In: Current Stem Cell Research and Therapy, Vol. 9, No. 4, 2014, p. 354-63.

Research output: Contribution to journalArticleResearchpeer-review

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AU - O'Neill, Helen C

AU - Griffiths, Kristin L

AU - Periasamy, Pravin

AU - Hinton, Rebecca A

AU - Petvises, Sawang

AU - Hey, Ying-ying

AU - Tan, Jonathan K H

PY - 2014

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AB - Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of stromal niches producing cells of multiple lineages. Limited success has been achieved in the past with induction of hematopoiesis in vitro. Previously, spleen long-term stromal cultures (LTC) were shown to continuously support restricted hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo equivalent dendritic cell type was then described which is specific for spleen. The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like CD11c(lo)CD11b(hi)CD8α-MHC-II- cell which differs phenotypically and functionally from monocytes/macrophages and conventional and plasmacytoid DC. Splenic stroma is now shown to maintain HSPC and to support their restricted in vitro differentiation to give this 'L-DC' subset. In order to characterise progenitors of this distinct cell type, LTC were analysed for cell subsets produced, and these subsets sorted and assessed for hematopoietic potential in subsequent co-cultures over STX3 stroma. Progenitors were defined as a lineage (Lin)(-)ckit(lo) subset reflecting HSPC. Furthermore, when Lin(-)ckit(hi)Sca1(+)Flt3(-) HSPC were sorted from bone marrow, they colonised splenic stroma with long-term production of L-DC. The maintenance of HSPC by splenic stroma was confirmed when non-adherent cells collected from LTC showed oligopotent reconstitution of the hematopoietic compartment of lethally irradiated mice. All data support a model whereby spleen houses a niche for HSPC in the resting state, with production of progenitors, and their differentiation to give tissue-specific antigen presenting cells.

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SN - 1574-888X

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