Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
An inner nuclear membrane protein induces rapid differentiation of human induced pluripotent stem cells
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.ORCID-id: 0000-0002-5556-7966
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.ORCID-id: 0000-0003-1287-0495
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
Vise andre og tillknytning
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Forskningsprogram
neurokemi med molekylär neurobiologi
Identifikatorer
URN: urn:nbn:se:su:diva-135805OAI: oai:DiVA.org:su-135805DiVA, id: diva2:1049180
Forskningsfinansiär
Swedish Research CouncilSwedish Cancer SocietyTilgjengelig fra: 2016-11-23 Laget: 2016-11-23 Sist oppdatert: 2017-04-27bibliografisk kontrollert
Inngår i avhandling
1. The role of nuclear membrane proteins in differentiation and chromatin organization
Åpne denne publikasjonen i ny fane eller vindu >>The role of nuclear membrane proteins in differentiation and chromatin organization
2016 (engelsk)Licentiatavhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The nuclear envelope, consisting of an outer and an inner nuclear membrane, surrounds the genomic material. The genomic material (chromatin) is highly structured with (transcriptionally inactive) heterochromatin mostly found in the nuclear periphery and (transcriptionally active) euchromatin mostly found in the nuclear interior. Underlying the nuclear envelope is the nuclear lamina that consists of lamin proteins and nuclear envelope transmembrane proteins (NETs), which organize chromatin in the nuclear periphery. There are several hundred uncharacterized tissue-specific NETs, with only a few linked to cellular differentiation. Induced pluripotent stem cells (iPSCs) enable studies of early differentiation and are a promising tool for cell replacement therapies.

In this licentiate thesis, we have focused on investigating the role of the inner nuclear membrane protein Samp1 in chromatin organization and cell differentiation. Overexpression of Samp1 induced a fast differentiation of iPSCs, suggesting that Samp1 may be involved in the differentiation process. We have also developed a novel image analysis method to be able to monitor chromatin organization in live cells. Depletion of Samp1 affected chromatin distribution and resulted in increased formation of peripheral heterochromatin, contradictory to what is expected of other characterized NETs. It is possible that Samp1 might have a role in both differentiation and chromatin organization and that future studies might link these two processes together.

sted, utgiver, år, opplag, sider
Stockholm: US-AB, 2016. s. 36
Emneord
nuclear membrane proteins, chromatin organization, epigenetics, differentiation, stem cells
HSV kategori
Forskningsprogram
neurokemi med molekylär neurobiologi
Identifikatorer
urn:nbn:se:su:diva-135773 (URN)978-91-7649-632-9 (ISBN)
Presentation
2016-12-20, Heilbronnsalen, C458, Svante Arrhenius väg 16B, Stockholm, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2016-11-23 Laget: 2016-11-22 Sist oppdatert: 2016-11-23bibliografisk kontrollert
2. Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
Åpne denne publikasjonen i ny fane eller vindu >>Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The eukaryotic nuclear envelope (NE), separates the nucleoplasm from cytoplasm and is made up of two concentric lipid membranes, the outer and the inner nuclear membranes (ONM and INM), the nuclear pore complexes (NPCs) and an underlying filamentous nuclear lamina. The INM contains hundreds of unique transmembrane proteins of which only a handful have been characterized. In this thesis, I aimed to understand the functional organization of proteins in the nuclear envelope and I focused on investigating the functions of a recently identified INM transmembrane protein, Samp1. We have developed a novel and robust approach, MCLIP, to identify specific protein-protein interactions taking place in live cells. Using MCLIP, we have shown that Samp1 interacts with proteins of the LINC complex, the nuclear lamina and components of the mitotic spindle. Samp1's specific interactions with a variety of binding partners, suggest that Samp1 plays important roles both in interphase and in mitosis.  We have also shown that Samp1 can provide a binding site at the INM for the GTPase Ran, a master regulator of protein interactions in interphase and in mitosis. Furthermore, we have also investigated the role of Samp1 in cell differentiation using two independent model systems. In human iPSCs, ectopic expression of Samp1 promoted differentiation despite pluripotent culture conditions. In C2C12 myoblast, depletion of Samp1 completely blocked differentiation into myotubes. The two studies complement each other and suggest that Samp1 has a strong differentiation promoting activity. Taken together, the findings in this thesis, give insights on the unexpected and unforeseen roles played by a transmembrane protein in different fundamental cellular process.

sted, utgiver, år, opplag, sider
Stockholm: Department of Neurochemistry, Stockholm University, 2017. s. 46
Emneord
Nuclear envelope, transmembrane protein interaction studies, cell differentiation, stem cells, myopathies
HSV kategori
Forskningsprogram
neurokemi med molekylär neurobiologi
Identifikatorer
urn:nbn:se:su:diva-141816 (URN)978-91-7649-577-3 (ISBN)978-91-7649-578-0 (ISBN)
Disputas
2017-05-31, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript.

Tilgjengelig fra: 2017-05-08 Laget: 2017-04-19 Sist oppdatert: 2018-06-19bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Søk i DiVA

Av forfatter/redaktør
Bergqvist, CeciliaJafferali, Mohammed HakimHallberg, Einar
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric

urn-nbn
Totalt: 305 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf