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Novel Skeletal Stem and Progenitor Cells and Their Regulation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Novel Skeletal Stem and Progenitor Cells and Their Regulation./
作者:	Zhou, Baoyi.
面頁冊數:	1 online resource (48 pages)
附註:	Source: Dissertations Abstracts International, Volume: 83-10, Section: A.
Contained By:	Dissertations Abstracts International83-10A.
標題:	Growth hormones. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29040227click for full text (PQDT)
ISBN:	9798209929369

Novel Skeletal Stem and Progenitor Cells and Their Regulation.
Zhou, Baoyi.

Novel Skeletal Stem and Progenitor Cells and Their Regulation. - 1 online resource (48 pages)

Source: Dissertations Abstracts International, Volume: 83-10, Section: A.

Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2022.

Includes bibliographical references

The development of bone and cartilage, which provide the framework of the skeletal system,is complex. In this context stem and progenitor cells play a crucial role by producingdifferentiated cells. Hormones are important regulators of this process, with growth hormone(GH) acting as the major endocrine regulator of longitudinal bone growth. In the presentthesis, I have studied primarily the stem and progenitor cells in the skeletal system, as well astheir regulation by GH.During embryonic development, all chondrocytes and bone-forming cells originate frommesodermal or neural crest cells (NCCs). As direct descendants of the NCCs, multipotentSchwann cell precursors (SCPs) generate a variety of cell and tissue types. Employinglineage tracing, we demonstrated that during embryonic development SCPs contribute to theproduction of significant numbers of skeletogenic cells in bone and cartilage. These SCPsdetach from the nerve fibers to become mesenchymal-type cells, which later differentiate intochondrocytes and osteocytes in the skeleton of the craniofacial region and scapula and ribs ofthe trunk. Our similar observations in zebrafish indicate that this process has been conservedevolutionarily. In summary, this work revealed a novel source of skeletogenic cells, as well aspotential interaction between the neurological and skeletal systems during development.(Paper I)Clonal lineage tracing with multicolor reporter mouse strains, including Confetti mice,provides a powerful tool for the study of cell behavior in vivo. However, it is challenging tomaintain the fluorescent signals until they can be analyzed, especially in the case ofmineralized tissues. Accordingly, we optimized a protocol that employs the Confetti model topreserve the fluorescent signals in postnatal bone tissues and visualize these directly byconfocal microscopy, without additional use of antibodies. (Paper IIDuring development, endochondral bone formation is driven primarily by a continuoussupply of chondrocytes provided by the growth plate. Employing lineage tracing inmulticolor reporter mice, we demonstrated that during fetal and neonatal development, theproduction of chondrocytes involves consumption of their progenitors, while at a laterpostnatal stage, these cells acquire the capacity for self-renewal. These findings indicate theformation of a novel stem cell niche that harbors the stem cells and facilitates their renewal.Moreover, we could show that the formation and maintenance of this niche depends to a largeextent on formation of the SOC. We also found that the switch between symmetrical andasymmetrical division of these stem cells, hereafter referred to as epiphyseal stem cells(epSCs), is regulated by the mTORC1 signaling pathway. (Paper III)Although GH is the primary endocrine regulator of longitudinal bone growth, the effects ofthis hormone on our newly identified epiphyseal stem cells and their niche were unknown.Using lineage tracing, we discovered that the renewal of epSCs in the growth plate involvespopulation asymmetry and neutral competition. GH activated the JAK-STAT pathway in epSCs and the number of these cells was reduced during continuous treatment with GH.Further analysis revealed that GH stimulates epSCs to leave their niche and generate progeny.Single-cell RNA sequencing (scRNA-seq) of all cells within the growth plate furtherconfirmed this shift of epSCs toward differentiation into transit-amplifying cells and, at thesame time, revealed that several molecular pathways are involved in the regulation of epSCsby GH, including local BMP, IGF and GAS signaling. (Paper IV)Altogether, my findings demonstrate that during development Schwann cell precursorsgenerate chondro- and osteo-progenitors. I developed a protocol for multi-color clonallineage tracing in mineralized tissues and applied this protocol to discover a novel stem cellniche within the epiphyseal growth plate. Finally, I characterized the dynamics and regulationof the stem cells by GH within this novel niche.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798209929369Subjects--Topical Terms:

3680868
Growth hormones.
Index Terms--Genre/Form:

542853
Electronic books.

Novel Skeletal Stem and Progenitor Cells and Their Regulation.
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520 $a The development of bone and cartilage, which provide the framework of the skeletal system,is complex. In this context stem and progenitor cells play a crucial role by producingdifferentiated cells. Hormones are important regulators of this process, with growth hormone(GH) acting as the major endocrine regulator of longitudinal bone growth. In the presentthesis, I have studied primarily the stem and progenitor cells in the skeletal system, as well astheir regulation by GH.During embryonic development, all chondrocytes and bone-forming cells originate frommesodermal or neural crest cells (NCCs). As direct descendants of the NCCs, multipotentSchwann cell precursors (SCPs) generate a variety of cell and tissue types. Employinglineage tracing, we demonstrated that during embryonic development SCPs contribute to theproduction of significant numbers of skeletogenic cells in bone and cartilage. These SCPsdetach from the nerve fibers to become mesenchymal-type cells, which later differentiate intochondrocytes and osteocytes in the skeleton of the craniofacial region and scapula and ribs ofthe trunk. Our similar observations in zebrafish indicate that this process has been conservedevolutionarily. In summary, this work revealed a novel source of skeletogenic cells, as well aspotential interaction between the neurological and skeletal systems during development.(Paper I)Clonal lineage tracing with multicolor reporter mouse strains, including Confetti mice,provides a powerful tool for the study of cell behavior in vivo. However, it is challenging tomaintain the fluorescent signals until they can be analyzed, especially in the case ofmineralized tissues. Accordingly, we optimized a protocol that employs the Confetti model topreserve the fluorescent signals in postnatal bone tissues and visualize these directly byconfocal microscopy, without additional use of antibodies. (Paper IIDuring development, endochondral bone formation is driven primarily by a continuoussupply of chondrocytes provided by the growth plate. Employing lineage tracing inmulticolor reporter mice, we demonstrated that during fetal and neonatal development, theproduction of chondrocytes involves consumption of their progenitors, while at a laterpostnatal stage, these cells acquire the capacity for self-renewal. These findings indicate theformation of a novel stem cell niche that harbors the stem cells and facilitates their renewal.Moreover, we could show that the formation and maintenance of this niche depends to a largeextent on formation of the SOC. We also found that the switch between symmetrical andasymmetrical division of these stem cells, hereafter referred to as epiphyseal stem cells(epSCs), is regulated by the mTORC1 signaling pathway. (Paper III)Although GH is the primary endocrine regulator of longitudinal bone growth, the effects ofthis hormone on our newly identified epiphyseal stem cells and their niche were unknown.Using lineage tracing, we discovered that the renewal of epSCs in the growth plate involvespopulation asymmetry and neutral competition. GH activated the JAK-STAT pathway in epSCs and the number of these cells was reduced during continuous treatment with GH.Further analysis revealed that GH stimulates epSCs to leave their niche and generate progeny.Single-cell RNA sequencing (scRNA-seq) of all cells within the growth plate furtherconfirmed this shift of epSCs toward differentiation into transit-amplifying cells and, at thesame time, revealed that several molecular pathways are involved in the regulation of epSCsby GH, including local BMP, IGF and GAS signaling. (Paper IV)Altogether, my findings demonstrate that during development Schwann cell precursorsgenerate chondro- and osteo-progenitors. I developed a protocol for multi-color clonallineage tracing in mineralized tissues and applied this protocol to discover a novel stem cellniche within the epiphyseal growth plate. Finally, I characterized the dynamics and regulationof the stem cells by GH within this novel niche.
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