Expression of KIT in the ovary, and the role of somatic precursor cells

Claudia Merkwitz, Paul Lochhead, Nika Tsikolia, Daniela Koch, Katja Sygnecka, Michiharu Sakurai, Katharina Spanel-Borowski, Albert M Ricken

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

KIT is a type III receptor protein tyrosine kinase, and KITL its cognate ligand. KIT can mediate its effects via several intracellular signalling pathways, or by formation of a cell-cell anchor with its ligand. Through these mechanisms, KIT controls fundamental cellular processes, including migration, proliferation, differentiation and survival. These cellular processes are modulated by soluble KIT, a cleavage product of KIT, generated at the cell membrane. A cell-retained KIT cleavage fragment also arises from this cleavage event. This cleavage fragment must be distinguished from truncated KIT (trKIT), which originates through cryptic promoter usage. The expression of trKIT is highly restricted to postmeiotic germ cells in the testis. In contrast, KIT, together with its cleavage products, is present in somatic cells and germ cells in the gonads of both sexes. A functional KITL/KIT system is mandatory for normal population of the gonads by germ cells. Signalling via the KITL/KIT system promotes the growth, maturation, and survival of germ cells within the gonads, and prevents meiotic entry and progression. In addition to its importance in germ cell biology, the KITL/KIT system is crucial for gonadal stromal differentiation. During foetal life, KIT is expressed by testicular stromal precursor cells, which develop into Leydig cells. In the ovary, stromal cell KIT expression accompanies theca layer development around advanced follicles. After ovulation, KIT-immunopositive cells translocate from the theca layer to the luteal ganulosa where they contribute to a delicate cellular network that extends between the fully luteinised large luteal cells. In the outer regions of the developing corpus luteum, a highly conspicuous subpopulation of KIT/CD14-double-immunopositive cells can be observed. KIT/CD14-double-immunopositive cells are also seen in the haematopoietic-like colonies of long-term granulosa cultures established from late antral follicles. These cultures demonstrate expression of pluripotency marker genes such as octamer binding transcription factor-3/4 and sex determining region Y-box 2. The KIT/CD14-double-immunopositive cells can be purified and enriched by KIT-immunopositive magnetic cell sorting. Subsequent exposure of the KIT-expressing cells to the hanging drop culture method, combined with haematopoietic differentiation medium, provides the signals necessary for their differentiation into endothelial and steroidogenic cells. This suggests that monocyte-derived multipotent cells are involved in ovarian tissue remodelling. In summary, multicelluar KITL/KIT signalling organizes the stroma in the ovary and testis; monocyte-derived multipotent cells may be involved.
Original languageEnglish
Pages (from-to)131-184
Number of pages54
JournalProgress in histochemistry and cytochemistry
Volume46
Issue number3
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Ovary
Cells
Germ Cells
Gonads
Transcription Factor 3
Cytology
Ligands
Corpus Luteum
Stromal Cells
Receptor Protein-Tyrosine Kinases
Cell membranes
Anchors
Sorting
Cell culture
Testis
Monocytes
Octamer Transcription Factor-3
Genes
Theca Cells
Luteal Cells

Keywords

  • animals
  • cell differentiation
  • corpus luteum
  • female
  • gametogenesis
  • germ cells
  • gonads
  • humans
  • leydig cells
  • male
  • ovary
  • proto-oncogene proteins c-kit
  • signal transduction
  • testis

Cite this

Merkwitz, C., Lochhead, P., Tsikolia, N., Koch, D., Sygnecka, K., Sakurai, M., ... Ricken, A. M. (2011). Expression of KIT in the ovary, and the role of somatic precursor cells. Progress in histochemistry and cytochemistry, 46(3), 131-184. https://doi.org/10.1016/j.proghi.2011.09.001

Expression of KIT in the ovary, and the role of somatic precursor cells. / Merkwitz, Claudia; Lochhead, Paul; Tsikolia, Nika; Koch, Daniela; Sygnecka, Katja; Sakurai, Michiharu; Spanel-Borowski, Katharina; Ricken, Albert M.

In: Progress in histochemistry and cytochemistry, Vol. 46, No. 3, 11.2011, p. 131-184.

Research output: Contribution to journalArticle

Merkwitz, C, Lochhead, P, Tsikolia, N, Koch, D, Sygnecka, K, Sakurai, M, Spanel-Borowski, K & Ricken, AM 2011, 'Expression of KIT in the ovary, and the role of somatic precursor cells', Progress in histochemistry and cytochemistry, vol. 46, no. 3, pp. 131-184. https://doi.org/10.1016/j.proghi.2011.09.001
Merkwitz, Claudia ; Lochhead, Paul ; Tsikolia, Nika ; Koch, Daniela ; Sygnecka, Katja ; Sakurai, Michiharu ; Spanel-Borowski, Katharina ; Ricken, Albert M. / Expression of KIT in the ovary, and the role of somatic precursor cells. In: Progress in histochemistry and cytochemistry. 2011 ; Vol. 46, No. 3. pp. 131-184.
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AU - Merkwitz, Claudia

AU - Lochhead, Paul

AU - Tsikolia, Nika

AU - Koch, Daniela

AU - Sygnecka, Katja

AU - Sakurai, Michiharu

AU - Spanel-Borowski, Katharina

AU - Ricken, Albert M

N1 - Copyright © 2011 Elsevier GmbH. All rights reserved.

PY - 2011/11

Y1 - 2011/11

N2 - KIT is a type III receptor protein tyrosine kinase, and KITL its cognate ligand. KIT can mediate its effects via several intracellular signalling pathways, or by formation of a cell-cell anchor with its ligand. Through these mechanisms, KIT controls fundamental cellular processes, including migration, proliferation, differentiation and survival. These cellular processes are modulated by soluble KIT, a cleavage product of KIT, generated at the cell membrane. A cell-retained KIT cleavage fragment also arises from this cleavage event. This cleavage fragment must be distinguished from truncated KIT (trKIT), which originates through cryptic promoter usage. The expression of trKIT is highly restricted to postmeiotic germ cells in the testis. In contrast, KIT, together with its cleavage products, is present in somatic cells and germ cells in the gonads of both sexes. A functional KITL/KIT system is mandatory for normal population of the gonads by germ cells. Signalling via the KITL/KIT system promotes the growth, maturation, and survival of germ cells within the gonads, and prevents meiotic entry and progression. In addition to its importance in germ cell biology, the KITL/KIT system is crucial for gonadal stromal differentiation. During foetal life, KIT is expressed by testicular stromal precursor cells, which develop into Leydig cells. In the ovary, stromal cell KIT expression accompanies theca layer development around advanced follicles. After ovulation, KIT-immunopositive cells translocate from the theca layer to the luteal ganulosa where they contribute to a delicate cellular network that extends between the fully luteinised large luteal cells. In the outer regions of the developing corpus luteum, a highly conspicuous subpopulation of KIT/CD14-double-immunopositive cells can be observed. KIT/CD14-double-immunopositive cells are also seen in the haematopoietic-like colonies of long-term granulosa cultures established from late antral follicles. These cultures demonstrate expression of pluripotency marker genes such as octamer binding transcription factor-3/4 and sex determining region Y-box 2. The KIT/CD14-double-immunopositive cells can be purified and enriched by KIT-immunopositive magnetic cell sorting. Subsequent exposure of the KIT-expressing cells to the hanging drop culture method, combined with haematopoietic differentiation medium, provides the signals necessary for their differentiation into endothelial and steroidogenic cells. This suggests that monocyte-derived multipotent cells are involved in ovarian tissue remodelling. In summary, multicelluar KITL/KIT signalling organizes the stroma in the ovary and testis; monocyte-derived multipotent cells may be involved.

AB - KIT is a type III receptor protein tyrosine kinase, and KITL its cognate ligand. KIT can mediate its effects via several intracellular signalling pathways, or by formation of a cell-cell anchor with its ligand. Through these mechanisms, KIT controls fundamental cellular processes, including migration, proliferation, differentiation and survival. These cellular processes are modulated by soluble KIT, a cleavage product of KIT, generated at the cell membrane. A cell-retained KIT cleavage fragment also arises from this cleavage event. This cleavage fragment must be distinguished from truncated KIT (trKIT), which originates through cryptic promoter usage. The expression of trKIT is highly restricted to postmeiotic germ cells in the testis. In contrast, KIT, together with its cleavage products, is present in somatic cells and germ cells in the gonads of both sexes. A functional KITL/KIT system is mandatory for normal population of the gonads by germ cells. Signalling via the KITL/KIT system promotes the growth, maturation, and survival of germ cells within the gonads, and prevents meiotic entry and progression. In addition to its importance in germ cell biology, the KITL/KIT system is crucial for gonadal stromal differentiation. During foetal life, KIT is expressed by testicular stromal precursor cells, which develop into Leydig cells. In the ovary, stromal cell KIT expression accompanies theca layer development around advanced follicles. After ovulation, KIT-immunopositive cells translocate from the theca layer to the luteal ganulosa where they contribute to a delicate cellular network that extends between the fully luteinised large luteal cells. In the outer regions of the developing corpus luteum, a highly conspicuous subpopulation of KIT/CD14-double-immunopositive cells can be observed. KIT/CD14-double-immunopositive cells are also seen in the haematopoietic-like colonies of long-term granulosa cultures established from late antral follicles. These cultures demonstrate expression of pluripotency marker genes such as octamer binding transcription factor-3/4 and sex determining region Y-box 2. The KIT/CD14-double-immunopositive cells can be purified and enriched by KIT-immunopositive magnetic cell sorting. Subsequent exposure of the KIT-expressing cells to the hanging drop culture method, combined with haematopoietic differentiation medium, provides the signals necessary for their differentiation into endothelial and steroidogenic cells. This suggests that monocyte-derived multipotent cells are involved in ovarian tissue remodelling. In summary, multicelluar KITL/KIT signalling organizes the stroma in the ovary and testis; monocyte-derived multipotent cells may be involved.

KW - animals

KW - cell differentiation

KW - corpus luteum

KW - female

KW - gametogenesis

KW - germ cells

KW - gonads

KW - humans

KW - leydig cells

KW - male

KW - ovary

KW - proto-oncogene proteins c-kit

KW - signal transduction

KW - testis

U2 - 10.1016/j.proghi.2011.09.001

DO - 10.1016/j.proghi.2011.09.001

M3 - Article

VL - 46

SP - 131

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JO - Progress in histochemistry and cytochemistry

JF - Progress in histochemistry and cytochemistry

SN - 1873-2186

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