Germ cell Biology, Developmental programming and Epigenetic inheritance of PCOS

Our lab is interested in understanding the developmental principles of the germline in health and disease. Moreover, we focus on how the parental effects are transmitted via developmental programming and germline moderation to future offspring, a process known as epigenetic inheritance. High-throughput sequencing, stem cell differentiation modeling, 3D organoid culture and transgenic mouse models are our frequently used tools among others.

Current projects

Characterization of the spatiotemporal regulation of epigenetic resetting and clonal propagation of germ cells

We want to address the fundamental questions: how epigenetic resetting including X-chromosome activation is coordinated with migration? Does it exist clonal behavior during germ cell formation? With advance of technology including cellular barcoding and single-cell technology, we want to reveal the principles underlying the stringent quality assurance of the germline, which is often derailed in germ cell tumors.

In vitro differentiation of germ cells towards maturation for disease modelling

In vitro directed differentiation assay serves as a platform to model germline formation, understand causes of infertility and reveal genetic and epigenetic errors that originate in the germline. We are currently establishing a stabilized pluripotency condition for primordial germ cell-like cell (PGCLC) specification and using iPSCs derived for disease modelling such as Klinefelter syndrome.

Transgenerational developmental programming and germline epigenetics.

We are using PCOS-like mouse models to study the adverse maternal health condition such as hyperandrogenism on transgenerational developmental programming and germline epigenetic moderation. We are now investigating the molecular details underlying the disease transmission and disentangling the effects between uterine environment and the germline reprogramming. This work is in close collaboration with Prof. Elisabet Stener-Victorin.

Molecular and functional characterization of maternal-fetal interaction in PCOS

Functional placentation and endometrial receptivity are essential to maintain a healthy pregnancy and support fetal development. Maternal PCOS condition due to hyperandrogenism is associated with miscarriage, preterm delivery and perinatal mortality. We aim to use both mouse models and human material together with single-cell sequencing and organoid culture to dissect the molecular signature of disease in placenta and endometrium for future targeted therapy. This work is in close collaboration with Prof. Elisabet Stener-Victorin.

 

Group members

Qiaolin Deng – Group Leader, PhD, Assistant Professor

Sanjiv Risal – Research specialist

Han-pin Pui – Postdoc

Veeramohan Veerapadian –Postdoc

Ahmed Reda – Postdoc

Yu Pei – Research Assistant

Qing Luo-doctoral student

Alumni

Geng Chen – Postdoc

Julia Aguila-Benitez – Postdoc

Marlene Yilmaz – Student

Mathias Ahlqvist – Student

Available positions

Postdoctoral position is available in in research areas of stem cell modeling, reproductive biology, and single-cell analysis. Master project students are always welcome.

Research funding

  • Swedish Research Council (VR)
  • Swedish Association for Medical Research (SSMF)
  • Karolinska Institutet faculty funding
  • Karolinska Institutet KID funding
  • Jeanssons Stiftelser
  • Åke Wiberg Stiftelser
  • The Kunt and Alice Wallenberg foundation
  • The Strategic Research Area in stem cells and regenerative medicine
  • Birgitta and Carl-Axel Rydbeck’s Research grant
  • KI-China Scholarship Council program

Selected publications

Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice.
Manti M*, Pui HP*, Edström S, Risal S, Lu H, Lindgren E, Ohlsson C, Jerlhag E, Benrick A, Deng Q#, Stener-Victorin E#
The FASEB Journal. 2020 Nov;34(11):14440-14457. * co-first author, #co-correspondence

LCM-seq reveals unique transcriptional adaptation mechanisms of resistant neurons and identifies protective pathways in spinal muscular atrophy.
Nichterwitz S, Nijssen J, Storvall H, Schweingruber C, Comley LH, Allodi I, Lee MV, Deng Q, Sandberg R, Hedlund E.Genome
Res. 2020 Aug;30(8):1083-1096.

Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome.
Risal S*, Pei Y*, Lu H*, Manti M, Fornes R, Pui HP, Zhao Z, Massart J, Ohlsson C, Lindgren E, Crisosto N, Maliqueo M, Echiburú B, Ladrón de Guevara A, Sir-Petermann T, Larsson H, Rosenqvist MA, Cesta CE, Benrick A, Deng Q#, Stener-Victorin E#. 
Nat Med. 2019 Dec;25(12):1894-1904.* co-first author, #co-correspondence

Single-cell RNA-seq reveals cellular heterogeneity of pluripotency transition and X-chromosome dynamics during early mouse development.
Cheng S, Pei Y, He L, Peng G, Reinius B, Tam PPL, Jing N, Deng Q
Cell Reports, volume26, Issue 10, P2593-2607.E3, March 05, 2019

LCM-Seq: A Method for Spatial Transcriptomic Profiling Using Laser Capture Microdissection Coupled with PolyA-Based RNA Sequencing
Nichterwitz S, Benitez JA, Hoogstraaten R, Deng Q, Hedlund E
Methods Mol Biol. 2018;1649:95-110. doi: 10.1007/978-1-4939-7213-5_6.

Revealing dynamic allele-specific gene expression by single-cell transcriptomics
Aguila Benitez JC, Cheng S, Deng Q
Int J Biochem Cell Biol. 2017 Sep;90:155-160.

Single-cell RNA sequencing: technological advancement and biological applications
Hedlund E, Deng Q
Mol Aspects Med. 2018 Feb Volume 59, 36-46.

Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.
Reinius B*, Mold JE*, Ramsköld D, Deng Q, Johnsson P, Michaëlsson J, Frisén J, Sandberg R.
Nat Genet. 2016 Nov; 48(11): 1430-1435.co-first author

Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.
Chen G, Schell JP, Benitez JA, Petropoulos S, Yilmaz M, Reinius B, Alekseenko Z, Shi L,Hedlund E, Lanner F, Sandberg R, Deng Q.
Genome Res. 2016 Oct;26(10):1342-1354, Cover story

Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling.
Nichterwitz S*, Chen G*, Aguila Benitez J, Yilmaz M, Storvall H, Cao M, Sandberg R, Deng Q#,Hedlund E#.
Nat Commun. 2016 Jul 8;7:12139. doi: 10.1038/ncomms12139. * co-first author #co-correspondence

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human PreimplantationEmbryos.Petropoulos S* 
Edsgärd D*, Reinius B*, Deng Q, Panula SP, Codeluppi S, Plaza Reyes A, Linnarsson S, Sandberg R, Lanner F.
Cell. 2016 May 5;165(4):1012-26. *Equal contribution

Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
Deng Q*, Ramsköld D*, Reinius B, Sandberg R.
Science. 2014 Jan 10;343(6167):193-6 *Equal contribution

Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells.
Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, Daniels GA, Khrebtukova I, Loring JF, Laurent LC, Schroth GP, Sandberg R.
Nat Biotechnol. 2012 Aug;30(8):777-82.

Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development.
Deng Q, Andersson E, Hedlund E, Alekseenko Z, Coppola E, Panman L, Millonig JH, Brunet JF, Ericson J, Perlmann T.
Development. 2011 Aug;138(16):3399-408.

Identification of intrinsic determinants of midbrain dopamine neurons.
Andersson E*, Tryggvason U*, Deng Q*, Friling S, Alekseenko Z, Robert B, Perlmann T, Ericson J.
Cell. 2006 Jan 27;124(2):393-405. *Equal contribution

 

Qiaolin Deng

Researcher
C3 Department of Physiology and Pharmacology