AG Reichart/Lindberg
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Single-cell genomics
The heart tissue is composed of multiple different cell types such as cardiomyocytes, fibroblasts or macrophages. This cellular diversity is necessary for normal heart contractility, relaxation and excitability. Single cell techniques extract cell type-specific information by measuring the transcriptome of each cardiac cell type, which helps to unravel the genetic readouts from healthy and diseased hearts. This technique enables the dissection of compositional changes and heterogeneity within each cell type and -state (=cell subtypes). ScRNA-seq using droplet-based microfluidic combines high-throughput, good sensitivity, and wide applicability. However due to their cell size of 100x25μm, adult CMs are not compatible with droplet-based microfluidics scRNA-seq techniques. As the average diameter of CM nuclei is 8-12μm, single nucleus RNA sequencing (snRNA-seq) of heart tissue provides a robust alternative to scRNA-seq and captures data from all cardiac lineages – even from frozen tissues.
The 11 major cell types and representative marker genes of the adult human heart are depicted in a 2-dimensional representation using the Uniform Manifold Approximation and Projection, (UMAP). Each dot represents one captured nucleus. Modified from Nature, 588, p 466–72 (2020).
Gene editing
Nucleic acid therapies are potential therapeutic approaches for cardiovascular genetic diseases. DNA modification can be achieved with genome editors delivered by vectors like adeno-associated viruses or liponanoparticles. CRISPR-based tools such as base or prime editing allow – even in post-mitotic cells – precise and efficient genome editing enabling modification of monogenetic cardiovascular diseases.
Three different types of CRISPR-based tools: nucleases, base and prime editors. Modified from Nature Biotechnology, 38, pages 824–44 (2020)
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Ausgewählte Publikationen
- Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies: Reichart D*, Lindberg EL*, Maatz H*, Miranda AMA, Viveiros A, Shvetsov N, Gärtner A, Nadelmann ER, Lee M, Kanemaru K, Ruiz-Orera J, Strohmenger V, DeLaughter DM, Patone G, Zhang H, Woehler A, Lippert C, Kim Y, Adami E, Gorham JM, Barnett SN, Brown K, Buchan RJ, Chowdhury RA, Constantinou C, Cranley J, Felkin LE, Fox H, Ghauri A, Gummert J, Kanda M, Li R, Mach L, McDonough B, Samari S, Shahriaran F, Yapp C, Stanasiuk C, Theotokis PI, Theis FJ, van den Bogaerdt A, Wakimoto H, Ware JS, Worth CL, Barton PJR, Lee YA, Teichmann SA, Milting H#, Noseda M#, Oudit GY#, Heinig M#, Seidman JG#, Hubner N#, Seidman CE#. Science. 2022 Aug 5;377(6606):eabo1984. doi: 10.1126/science.abo1984.
- Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice: Reichart D*, Newby GA*, Wakimoto H*, Lun M, Gorham JM, Curran JJ, Raguram A, DeLaughter DM, Conner DA, Marsiglia JDC, Kohli S, Chmatal L, Page DC, Zabaleta N, Vandenberghe L, Liu DR, Seidman JG, Seidman C., Nat Med. 2023 Feb;29(2):412-421. doi: 10.1038/s41591-022-02190-7.
- Cells of the adult human heart: Litviňuková M*, Talavera-López C*, Maatz H*, Reichart D*, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Roberts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bayraktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N, Teichmann SA.. Nature. 2020 Dec;588(7838):466-472. doi: 10.1038/s41586-020-2797-4.
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Dr. med. Daniel Reichart
AG Leiter
Mguliä Bilyzgpbvimsful_v,fiu:;yz:iu miDr.rer.nat. Eric Lindberg
AG Leiter
NplysVlumjipxviSmeful#vfi,uyziu miDr. med. Finn Becker
Medical Doctor and Postdoctoral Researcher
wluu jiyoipvimeful_vfiSuyz:i;utmiVladana Dakovic
Doktorandin
ÖägmagugtMgoüqlyvimefudl+vfiuyziu miFelix Feuchtinger
MD Student
wiälƒ ,wifyazbluxipvim ful_vDfiuyziutmYiLarissa Henkel
Doktorandin
VgplccgeZiuoiäavimsfuSl#vfiuyziu miNadine Jansen
MD Student
Tgmlui-Qguciuvim ful_v;fiuyziu-m,iHeike Kartmann
Lab Manager & Technical Assistant
ziloi ogpnbvguuvim ful_vf:iunyziusdmiMaximilian Kessler
Medical Doctor and Postdoctoral Researcher
Ogƒlvl,älgnu-Üiccäipvim:tful#vfiuYyziusmiAthina Lurz
Doktorandin
Fbzlug-Vfpß,vimsful_vfiuyziu-miMohammad Amine Noureddine
MD Student
nOüzgvim Tüfpimmlu:ivim fulWhvfiuyziu-m:iAlexandra Victoria Petkof
Doktorandin
FWäiƒgum;png Piboüwvimeful+vfiuyziud miConstanze Schmidt
MD Student
HüucbgußisRyzvlmbvim ful_vfiuyziusmiLouisa Weber
MD Student
Xin Zhang
Doktorand