Specific Cell (Re-)Programming: Approaches and Perspectives

  • Frauke Hausburg
  • Julia Jeannine Jung
  • Robert DavidEmail author
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 163)


Many disorders are manifested by dysfunction of key cell types or their disturbed integration in complex organs. Thereby, adult organ systems often bear restricted self-renewal potential and are incapable of achieving functional regeneration. This underlies the need for novel strategies in the field of cell (re-)programming-based regenerative medicine as well as for drug development in vitro. The regenerative field has been hampered by restricted availability of adult stem cells and the potentially hazardous features of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Moreover, ethical concerns and legal restrictions regarding the generation and use of ESCs still exist. The establishment of direct reprogramming protocols for various therapeutically valuable somatic cell types has overcome some of these limitations. Meanwhile, new perspectives for safe and efficient generation of different specified somatic cell types have emerged from numerous approaches relying on exogenous expression of lineage-specific transcription factors, coding and noncoding RNAs, and chemical compounds.

It should be of highest priority to develop protocols for the production of mature and physiologically functional cells with properties ideally matching those of their endogenous counterparts. Their availability can bring together basic research, drug screening, safety testing, and ultimately clinical trials. Here, we highlight the remarkable successes in cellular (re-)programming, which have greatly advanced the field of regenerative medicine in recent years. In particular, we review recent progress on the generation of cardiomyocyte subtypes, with a focus on cardiac pacemaker cells.

Graphical Abstract


Cardiovascular regeneration Cell fate conversion Direct reprogramming Lineage conversion Metabolic disorders Neurodegenerative disorders Regenerative medicine 



Ca2+ channel agonist


TGF-β inhibitor


Ascorbic acid




Adipose tissue-derived mesenchymal stem cell




AKT serine/threonine kinase 1




TGFβ type I receptor kinase


Alkaline phosphatase


NPPA, natriuretic peptide A


Action potential duration


Apolipoprotein A1


Iron chelator


Adult stem cell


Achaete-scute homolog 1


Activating transcription factor 5


Adipose tissue-derived mesenchymal stem cells




B-cell lymphoma 2


Bioartificial cardiac tissue


Basic fibroblast growth factor


Basic helix-loop-helix


6-Bromoindirubin-3′-oxime, canonical Wnt activator


Diazepin-quinazolinamine derivative; histone-lysine methyltransferase inhibitor


BMI1 proto-oncogene, polycomb ring finger


Bone marrow-derived mesenchymal stem cell


Beats per minute




ALCAM; activated leukocyte cell adhesion molecule


CCAAT/enhancer binding protein alpha


Cardiac fibroblast


Congenital heart defect


CHIR99021, GSK-3 inhibitor, Wnt activator




MYC proto-oncogene, bHLH transcription factor


Cardiac progenitor cell


Cardiac reprogramming medium


Conduction system


SHH and the GSK3β inhibitor


Troponin I3, cardiac type


Troponin T2, cardiac type


Gap junction protein


Cytochrome P450


N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester


Newborn neuron




Dermal fibroblast


Dental follicular-derived mesenchymal stem cell


Distal-less homeobox


Dulbecco’s modified eagle medium: nutrient mixture F-12




Early after depolarizations


1-EBIO; KCa2/3 channel activator


Epidermal growth factor


Endothelial progenitor cell


Epicardium-derived cell


Embryonic stem cell




Fibroblast growth factor


First heart field


Fetal limb fibroblast


Adenylyl cyclase activator


Forkhead box


Gamma-aminobutyric acid


Glutamate decarboxylase 1


GATA binding protein 4


Gingival fibroblast


SLC2A2; solute carrier family 2 member 2


Gata4, Mef2c & Tbx5


Gata4, Mef2c, Tbx5 & Hand2


PKC inhibitor


Selective EZH2 methyltransferase inhibitor


Heart and neural crest derivatives expressed 2




Human cardiac microvascular endothelial cell


Hyperpolarization-activated cyclic nucleotide channel


Human embryonic fibroblast


Human foreskin fibroblast


Induced pluripotent stem cell-derived embryonic cardiac myocyte


Hepatic nuclear factor


Bromodomain and extra-terminal domain family inhibitor


Funny current


Induced pluripotent stem cell


ISL LIM homeobox 1


Neurogenesis inducer



JAK inhibitor I

Janus-Associated Kinase Inhibitor I


ATP-competitive inhibitor of platelet-derived growth Factor receptor tyrosine kinase


C-Jun N-terminal kinases


Kruppel like factor 4


Low-density lipoprotein


BMP4 inhibitor


Lung fibroblast


LIM homeobox protein 6


Leukemia inhibiting factor, JAK/STAT activator


LIM homeobox transcription factor 1 alpha


MYCL proto-oncogene, bHLH transcription factor


Long noncoding RNA


Left ventricular ejection fraction


Phosphoinositide 3-kinase (PI3K) inhibitor, TGF-β activator


v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A


Microtubule-associated protein 2


Mitogen-activated protein kinase 1


Mouse embryonic fibroblast


Myocyte enhancer factor 2C




Myosin heavy chain


Myocardial infarction




Myosin, light polypeptide 2, regulatory, cardiac, slow


Combination of Gata4, Hand2, Tbx5, and the fusion gene MM3 between Mef2c and the transactivation domain of MyoD


Magnet resonance imaging


Mesenchymal stem cell


Embryonic myosin


Myosin heavy chain 6, cardiac muscle, alpha


Myosin heavy chain 6


Myogenic differentiation 1




Myelin transcription factor 1 like


Cysteine proteinase inhibitor


Neuronal nuclei


Neurogenic differentiation 1


Neuronal differentiation 2


Neonatal foreskin fibroblast


Oligodendrocyte precursor




Homeobox protein




Neonatal cardiac fibroblast


Neonatal fibroblast


Neonatal rat ventricular myocyte


Nuclear receptor related 1 protein


Oct4-activating compound 2






POU class 5 homeobox 1


Pacemaker cell


MEK1/2 inhibitor


Insulin promoter factor 1


Protein kinase C




prospero homeobox 1


Pluripotent stem cell






Inhibitor of the TGF-β type 1 receptor


Rho-associated protein kinase


Runt related transcription factor 2


Ryanodine receptor 2


Smoothened agonist


Sinoatrial node


TGF-β inhibitor


Stem cell


Pluripotin, dual selective inhibitor of the ERK1 and Ras-GAP signaling pathways


Sudden cardiac death


Sodium channel, voltage-gated, type V, alpha subunit


Serpin family A member 1


Second heart field


Sonic hedgehog


Short stature homeobox 2


Small hairpin RNA


Small interfering RNA


Signal regulatory protein alpha


Solute carrier family 1 member 2


Sex determining region Y-box 2


JNK inhibitor


ROCK inhibitor


Sick sinus syndrome


Signal transducer and activator of transcription 3


Platelet-derived growth factor receptor β inhibitor


Simian vacuolating virus 40


T-box factor 18


Transcription factor


Transforming growth factor-β


Tertiary heart field


Troponin T2, cardiac type


Tail tip fibroblast


Analog of retinoic acid




Neuron-specific class III beta-tubulin




Histone methyltransferase inhibitor


Vascular endothelial growth factor


Vesicular glutamate transporter 1


Valporic acid


Wnt inhibitor


ROCK inhibitor


Myosin heavy chain 6




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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Frauke Hausburg
    • 1
    • 2
  • Julia Jeannine Jung
    • 1
    • 2
  • Robert David
    • 1
    • 2
    Email author
  1. 1.Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac SurgeryRostock University Medical CenterRostockGermany
  2. 2.Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock UniversityRostockGermany

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