Spleen as a Site for Hematopoiesis

Hong Kiat (Don) Lim, Jonathan Tan, Helen C O'Neill

Research output: Contribution to journalMeeting AbstractResearchpeer-review

Abstract

Hematopoiesis occurs throughout the lifespan of an organism. This process involves the formation of blood cells from self-renewing hematopoietic stem cells (HSC). The hematopoietic niche environment, which comprises non-hematopoietic stromal cells, regulates the quiescence, dormancy, self-renewal and differentiation of HSC. It is known that multiple HSC niches including endosteal, vascular and perivascular exist in the bone marrow, although less is known for other sites like spleen. Previous studies in this lab have described unique splenic stromal cell lines 5G3 and 3B5 which can support restricted hematopoiesis in vitro reflecting HSC niches. Inhibition assays were also used to identify the important role of SCF and Notch but not CXCL12 in supporting in vitro hematopoiesis. Transcriptome data previously showed that 5G3 and 3B5 express many genes in parallel with perivascular cells described in bone marrow. The study here shows that both 5G3 and 3B5 stroma share lineage origin with perivascular cells in bone marrow, including mesenchymal stem cells and C-XC motif ligand 12 (CXCL12)-abundant reticular cells. 5G3 and 3B5 express cell surface markers in common with these cells including CD105, CD29, VCAM1, Sca-1, CD51, CD140a and Thy1.2. In addition, splenic stromal cells with the Sca-1 + gp38+Thy1.2 + CD29+CD51+ phenotype, reflecting cells of mesenchymal lineage were found to be important for in vitro hematopoiesis. Stromal cells expressing gp38 or Thy1.2 are also associated with HSC in spleen identified through section staining. Restricted hematopoiesis giving rise to specific types of myeloid cells was replicated in vivo following grafting of splenic stromal cell lines 5G3, 10C9 and 3B5 under the kidney capsule. This study has improved our understanding of HSC niches in spleen and identified several molecular regulators of hematopoiesis. Information obtained will be important for development therapies involving splenic or ectopic niches to enhance hematopoietic output, in immunocompromised patients or following HSC transplantation.
Original languageEnglish
Article number3091
Pages (from-to)S80
Number of pages1
JournalExperimental Hematology
Volume64
Issue numberSupplement
DOIs
Publication statusPublished - 22 Aug 2018
EventThe 47th Annual Scientific Meeting of the ISEH - International Society for Experimental Hematology - Luskin Conference Center, Los Angeles, United States
Duration: 23 Aug 201826 Aug 2018
Conference number: 47th
https://www.iseh.org/

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Hematopoiesis
Hematopoietic Stem Cells
Stromal Cells
Spleen
Stem Cell Niche
Bone Marrow
Ligands
Cell Line
Hematopoietic Stem Cell Transplantation
Immunocompromised Host
Cell Lineage
Myeloid Cells
Mesenchymal Stromal Cells
Transcriptome
Bone Marrow Cells
Capsules
Blood Vessels
Blood Cells
Staining and Labeling
Phenotype

Cite this

Lim, Hong Kiat (Don) ; Tan, Jonathan ; O'Neill, Helen C. / Spleen as a Site for Hematopoiesis. In: Experimental Hematology. 2018 ; Vol. 64, No. Supplement. pp. S80.
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title = "Spleen as a Site for Hematopoiesis",
abstract = "Hematopoiesis occurs throughout the lifespan of an organism. This process involves the formation of blood cells from self-renewing hematopoietic stem cells (HSC). The hematopoietic niche environment, which comprises non-hematopoietic stromal cells, regulates the quiescence, dormancy, self-renewal and differentiation of HSC. It is known that multiple HSC niches including endosteal, vascular and perivascular exist in the bone marrow, although less is known for other sites like spleen. Previous studies in this lab have described unique splenic stromal cell lines 5G3 and 3B5 which can support restricted hematopoiesis in vitro reflecting HSC niches. Inhibition assays were also used to identify the important role of SCF and Notch but not CXCL12 in supporting in vitro hematopoiesis. Transcriptome data previously showed that 5G3 and 3B5 express many genes in parallel with perivascular cells described in bone marrow. The study here shows that both 5G3 and 3B5 stroma share lineage origin with perivascular cells in bone marrow, including mesenchymal stem cells and C-XC motif ligand 12 (CXCL12)-abundant reticular cells. 5G3 and 3B5 express cell surface markers in common with these cells including CD105, CD29, VCAM1, Sca-1, CD51, CD140a and Thy1.2. In addition, splenic stromal cells with the Sca-1 + gp38+Thy1.2 + CD29+CD51+ phenotype, reflecting cells of mesenchymal lineage were found to be important for in vitro hematopoiesis. Stromal cells expressing gp38 or Thy1.2 are also associated with HSC in spleen identified through section staining. Restricted hematopoiesis giving rise to specific types of myeloid cells was replicated in vivo following grafting of splenic stromal cell lines 5G3, 10C9 and 3B5 under the kidney capsule. This study has improved our understanding of HSC niches in spleen and identified several molecular regulators of hematopoiesis. Information obtained will be important for development therapies involving splenic or ectopic niches to enhance hematopoietic output, in immunocompromised patients or following HSC transplantation.",
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Spleen as a Site for Hematopoiesis. / Lim, Hong Kiat (Don); Tan, Jonathan ; O'Neill, Helen C.

In: Experimental Hematology, Vol. 64, No. Supplement, 3091, 22.08.2018, p. S80.

Research output: Contribution to journalMeeting AbstractResearchpeer-review

TY - JOUR

T1 - Spleen as a Site for Hematopoiesis

AU - Lim, Hong Kiat (Don)

AU - Tan, Jonathan

AU - O'Neill, Helen C

PY - 2018/8/22

Y1 - 2018/8/22

N2 - Hematopoiesis occurs throughout the lifespan of an organism. This process involves the formation of blood cells from self-renewing hematopoietic stem cells (HSC). The hematopoietic niche environment, which comprises non-hematopoietic stromal cells, regulates the quiescence, dormancy, self-renewal and differentiation of HSC. It is known that multiple HSC niches including endosteal, vascular and perivascular exist in the bone marrow, although less is known for other sites like spleen. Previous studies in this lab have described unique splenic stromal cell lines 5G3 and 3B5 which can support restricted hematopoiesis in vitro reflecting HSC niches. Inhibition assays were also used to identify the important role of SCF and Notch but not CXCL12 in supporting in vitro hematopoiesis. Transcriptome data previously showed that 5G3 and 3B5 express many genes in parallel with perivascular cells described in bone marrow. The study here shows that both 5G3 and 3B5 stroma share lineage origin with perivascular cells in bone marrow, including mesenchymal stem cells and C-XC motif ligand 12 (CXCL12)-abundant reticular cells. 5G3 and 3B5 express cell surface markers in common with these cells including CD105, CD29, VCAM1, Sca-1, CD51, CD140a and Thy1.2. In addition, splenic stromal cells with the Sca-1 + gp38+Thy1.2 + CD29+CD51+ phenotype, reflecting cells of mesenchymal lineage were found to be important for in vitro hematopoiesis. Stromal cells expressing gp38 or Thy1.2 are also associated with HSC in spleen identified through section staining. Restricted hematopoiesis giving rise to specific types of myeloid cells was replicated in vivo following grafting of splenic stromal cell lines 5G3, 10C9 and 3B5 under the kidney capsule. This study has improved our understanding of HSC niches in spleen and identified several molecular regulators of hematopoiesis. Information obtained will be important for development therapies involving splenic or ectopic niches to enhance hematopoietic output, in immunocompromised patients or following HSC transplantation.

AB - Hematopoiesis occurs throughout the lifespan of an organism. This process involves the formation of blood cells from self-renewing hematopoietic stem cells (HSC). The hematopoietic niche environment, which comprises non-hematopoietic stromal cells, regulates the quiescence, dormancy, self-renewal and differentiation of HSC. It is known that multiple HSC niches including endosteal, vascular and perivascular exist in the bone marrow, although less is known for other sites like spleen. Previous studies in this lab have described unique splenic stromal cell lines 5G3 and 3B5 which can support restricted hematopoiesis in vitro reflecting HSC niches. Inhibition assays were also used to identify the important role of SCF and Notch but not CXCL12 in supporting in vitro hematopoiesis. Transcriptome data previously showed that 5G3 and 3B5 express many genes in parallel with perivascular cells described in bone marrow. The study here shows that both 5G3 and 3B5 stroma share lineage origin with perivascular cells in bone marrow, including mesenchymal stem cells and C-XC motif ligand 12 (CXCL12)-abundant reticular cells. 5G3 and 3B5 express cell surface markers in common with these cells including CD105, CD29, VCAM1, Sca-1, CD51, CD140a and Thy1.2. In addition, splenic stromal cells with the Sca-1 + gp38+Thy1.2 + CD29+CD51+ phenotype, reflecting cells of mesenchymal lineage were found to be important for in vitro hematopoiesis. Stromal cells expressing gp38 or Thy1.2 are also associated with HSC in spleen identified through section staining. Restricted hematopoiesis giving rise to specific types of myeloid cells was replicated in vivo following grafting of splenic stromal cell lines 5G3, 10C9 and 3B5 under the kidney capsule. This study has improved our understanding of HSC niches in spleen and identified several molecular regulators of hematopoiesis. Information obtained will be important for development therapies involving splenic or ectopic niches to enhance hematopoietic output, in immunocompromised patients or following HSC transplantation.

U2 - 10.1016/j.exphem.2018.06.277

DO - 10.1016/j.exphem.2018.06.277

M3 - Meeting Abstract

VL - 64

SP - S80

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - Supplement

M1 - 3091

ER -