Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
An inner nuclear membrane protein induces rapid differentiation of human induced pluripotent stem cells
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-5556-7966
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0003-1287-0495
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
National Category
Other Chemistry Topics Cell Biology
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
URN: urn:nbn:se:su:diva-135805OAI: oai:DiVA.org:su-135805DiVA: diva2:1049180
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2017-04-27Bibliographically approved
In thesis
1. The role of nuclear membrane proteins in differentiation and chromatin organization
Open this publication in new window or tab >>The role of nuclear membrane proteins in differentiation and chromatin organization
2016 (English)Licentiate thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Stockholm: US-AB, 2016. 36 p.
Keyword
nuclear membrane proteins, chromatin organization, epigenetics, differentiation, stem cells
National Category
Cell Biology Other Chemistry Topics
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
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 (English)
Opponent
Supervisors
Available from: 2016-11-23 Created: 2016-11-22 Last updated: 2016-11-23Bibliographically approved
2. Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
Open this publication in new window or tab >>Multifaceted roles of the transmembrane nuclear envelope protein, Samp1
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2017. 46 p.
Keyword
Nuclear envelope, transmembrane protein interaction studies, cell differentiation, stem cells, myopathies
National Category
Biochemistry and Molecular Biology Cell Biology Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-141816 (URN)978-91-7649-577-3 (ISBN)978-91-7649-578-0 (ISBN)
Public defence
2017-05-31, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

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.

Available from: 2017-05-08 Created: 2017-04-19 Last updated: 2017-06-02Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Bergqvist, CeciliaJafferali, Mohammed HakimHallberg, Einar
By organisation
Department of Neurochemistry
Other Chemistry TopicsCell Biology

Search outside of DiVA

GoogleGoogle Scholar

Total: 140 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf