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@ARTICLE{Wnsche:136836,
author = {P. Wünsche$^*$ and E. Eckert$^*$ and T. Holland-Letz$^*$
and A. Paruzynski and A. Hotz-Wagenblatt$^*$ and R.
Fronza$^*$ and T. Rath$^*$ and I. Gil-Farina$^*$ and M.
Schmidt$^*$ and C. von Kalle$^*$ and C. Klein and C.
Ball$^*$ and F. Herbst$^*$ and H. Glimm$^*$},
title = {{M}apping {A}ctive {G}ene-{R}egulatory {R}egions in {H}uman
{R}epopulating {L}ong-{T}erm {HSC}s.},
journal = {Cell stem cell},
volume = {23},
number = {1},
issn = {1934-5909},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2018-01274},
pages = {132 - 146.e9},
year = {2018},
abstract = {Genes that regulate hematopoietic stem cell (HSC)
self-renewal, proliferation, and differentiation are tightly
controlled by regulatory regions. However, mapping such
regions relies on surface markers and immunophenotypic
definition of HSCs. Here, we use γ-retroviral integration
sites (γRV ISs) from a gene therapy trial for 10 patients
with Wiskott-Aldrich syndrome to mark active enhancers and
promoters in functionally defined long-term repopulating
HSCs. Integration site clusters showed the highest ATAC-seq
signals at HSC-specific peaks and strongly correlated with
hematopoietic risk variants. Tagged genes were significantly
enriched for HSC gene sets. We were able to map over 3,000
HSC regulatory regions in late-contributing HSCs, and we
used these data to identify miR-10a and miR-335 as two
miRNAs regulating early hematopoiesis. In this study, we
show that viral insertion sites can be used as molecular
tags to assess chromatin conformation on functionally
defined cell populations, thereby providing a genome-wide
resource for regulatory regions in human repopulating
long-term HSCs.},
cin = {B280 / G100 / C060 / W610 / L301},
ddc = {570},
cid = {I:(DE-He78)B280-20160331 / I:(DE-He78)G100-20160331 /
I:(DE-He78)C060-20160331 / I:(DE-He78)W610-20160331 /
I:(DE-He78)L301-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29979988},
doi = {10.1016/j.stem.2018.06.003},
url = {https://inrepo02.dkfz.de/record/136836},
}