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Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis
Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
Karolinska Inst, Dept Clin Immunol, S-14186 Stockholm, Sweden..
Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
KTH, School of Biotechnology (BIO), Gene Technology.
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2015 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 22, no 3, 408-417 p.Article in journal (Refereed) Published
Abstract [en]

Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute similar to 10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects.

Place, publisher, year, edition, pages
2015. Vol. 22, no 3, 408-417 p.
National Category
Cell Biology Endocrinology and Diabetes
URN: urn:nbn:se:kth:diva-173762DOI: 10.1016/j.cmet.2015.06.011ISI: 000360453900013PubMedID: 26190649ScopusID: 2-s2.0-84940718419OAI: diva2:855910
Swedish Diabetes AssociationSwedish Cancer SocietySwedish Research CouncilNovo Nordisk
Available from: 2015-09-22 Created: 2015-09-18 Last updated: 2016-01-27Bibliographically approved
In thesis
1. Technologies for Single Cell Genome Analysis
Open this publication in new window or tab >>Technologies for Single Cell Genome Analysis
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During the last decade high throughput DNA sequencing of single cells has evolved from an idea to one of the most high profile fields of research. Much of this development has been possible due to the dramatic reduction in costs for massively parallel sequencing. The four papers included in this thesis describe or evaluate technological advancements for high throughput DNA sequencing of single cells and single molecules.

As the sequencing technologies improve, more samples are analyzed in parallel. In paper 1, an automated procedure for preparation of samples prior to massively parallel sequencing is presented. The method has been applied to several projects and further development by others has enabled even higher sample throughputs. Amplification of single cell genomes is a prerequisite for sequence analysis. Paper 2 evaluates four commercially available kits for whole genome amplification of single cells. The results show that coverage of the genome differs significantly among the protocols and as expected this has impact on the downstream analysis. In Paper 3, single cell genotyping by exome sequencing is used to confirm the presence of fat cells derived from donated bone marrow within the recipients’ fat tissue. Close to hundred single cells were exome sequenced and a subset was validated by whole genome sequencing. In the last paper, a new method for phasing (i.e. determining the physical connection of variant alleles) is presented. The method barcodes amplicons from single molecules in emulsion droplets. The barcodes can then be used to determine which variants were present on the same original DNA molecule. The method is applied to two variable regions in the bacterial 16S gene in a metagenomic sample.

Thus, two of the papers (1 and 4) present development of new methods for increasing the throughput and information content of data from massively parallel sequencing. Paper 2 evaluates and compares currently available methods and in paper 3, a biological question is answered using some of these tools.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. 48 p.
TRITA-BIO-Report, ISSN 1654-2312 ; 2016:1
DNA, sequencing, single molecule, single cell, whole genome amplification, exome sequencing, emulsions, barcoding, phasin
National Category
Bioinformatics and Systems Biology
Research subject
urn:nbn:se:kth:diva-181059 (URN)978-91-7595-842-2 (ISBN)
Public defence
2016-02-19, Air and Fire, Science for Life Laboratory, KTH, Tomtebodavägen 23A, Solna, 10:00 (English)

QC 20160127

Available from: 2016-01-27 Created: 2016-01-27 Last updated: 2016-01-27Bibliographically approved

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