PLURİPOTENT KÖK HÜCRELERDEN SİNİR HÜCRELERİNE FARKLILAŞTIRMA YÖNTEMLERİ
Year 2022,
Volume: 29 Issue: 4, 691 - 696, 27.12.2022
Meltem Kuruş
,
Kemal Ergin
,
Rahmi Çetinkaya
Abstract
İnsan embriyonik kök hücreleri, embriyoların erken
blastokist evresindeki iç hücre kütlesinden türetilen
hücrelerdir. Pluripotent özellikte olan bu hücreler, uygun
koşullar altında fonksiyonel nöronlara ve farklı
tipte sinir hücrelerine farklılaştırılabilmektedir. Ancak
bu alandaki en büyük zorluklardan biri, yenilenebilir,
kültürü kolay, nöral soylara bağlı nöral prekürsör
hücre popülasyonu oluşturmaktır. Bu nedenle, insan
embriyonik kök hücrelerini prekürsör hücrelere en
uygun şekilde farklılaştırmak, bunların kendi kendini
yenileyen bir popülasyon olarak devam etmesi ve
farklı bölgelerdeki sinir hücre tiplerini saf bir popülasyon
şeklinde üretmek için kritik öneme sahiptir. Hücre
sinyalleri ve bunlarla ilişkili moleküller de bu olaylarda
önemli bir rol oynamaktadır. Nöral prekürsör hücrelerinin
üretilmesi için kök hücre biyolojisinin ve nöral
hücrelere farklılaşmada rol oynayan önemli yolakların
daha iyi anlaşılması gerekmektedir. Bu derlemede
kök hücrelerden nöral hücrelere farklılaştırma yöntemlerine
ve bu süreçte önemli olan sinyal yolaklarına
ve moleküllere odaklanılmaktadır.
Supporting Institution
İzmir Katip Çelebi Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü
Project Number
2016-ÖNP-TIPF-0028
Thanks
İzmir Katip Çelebi Üniversitesi BAP birimi 2016-ÖNP-TIPF-0028 numaralı proje çerçevesince desteklerinden dolayı teşekkür ederiz.
References
- 1. Liu G, David BT, Trawczynski M, Fessler RG. Advances in Pluripotent
Stem Cells: History, Mechanisms, Technologies, and Applications. Stem Cell Rev Rep. 2020;16(1):3-32.
- 2. Zhang S, Bell E, Zhi H, Brown S, Imran SAM, Azuara V, Cui W.
OCT4 and PAX6 determine the dual function of SOX2 in human
ESCs as a key pluripotent or neural factor. Stem Cell Res Ther.
2019;10(1):122.
- 3. Elkabetz Y, Panagiotakos G, Al Shamy G, Socci ND, Tabar
V, Studer L. Human ES cell-derived neural rosettes reveal a
functionally distinct early neural stem cell stage. Genes Dev.
2008;22(2):152-65.
- 4. Selvaraj V, Jiang P, Chechneva O, Lo UG, Deng W. Differentiating
human stem cells into neurons and glial cells for neural
repair. Front Biosci (Landmark Ed). 2012;17:65-89.
- 5. Perrier AL, Tabar V, Barberi T, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl
Acad Sci USA. 2004;101(34):12543-8.
- 6. Mizuseki K, Sakamoto T, Watanabe K, Muguruma K, Ikeya
M, Nishiyama A, Arakawa A, Suemori H, Nakatsuji N, Kawasaki
H, Murakami F, Sasai Y. Generation of neural crest-derived
peripheral neurons and floor plate cells from mouse
and primate embryonic stem cells. Proc Natl Acad Sci U S A.
2003;100(10):5828-33.
- 7. Roy NS, Cleren C, Singh SK, Yang L, Beal MF, Goldman
SA.(2006) Functional engraftment of human ES cell-derived
dopaminergic neurons enriched by coculture with telomerase-
immortalized midbrain astrocytes Nat Med 12, 1259–68.
- 8. Yang D, Zhang ZJ, Oldenburg M, Ayala M, Zhang SC. Human
embryonic stem cell-derived dopaminergic neurons
reverse functional deficit in parkinsonian rats. Stem Cells.
2008;26(1):55-63.
- 9. Pekny M, Pekna M, Messing A, et al. Astrocytes: a central
element in neurological diseases. Acta Neuropathol.
2016;131(3):323-345.
- 10. Krencik R, Zhang SC. Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc.
2011;6(11):1710-1717.
- 11. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M,
Sadelain M, Studer L. Highly efficient neural conversion of
human ES and iPS cells by dual inhibition of SMAD signaling
[published correction appears in Nat Biotechnol. 2009
May;27(5):485]. Nat Biotechnol. 2009;27(3):275-280.
- 12. Zhang SC, Wernig M, Duncan ID, Brüstle O, Thomson JA. In
vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001;19(12):1129-
1133.
- 13. Hu BY, Weick JP, Yu J, et al. Neural differentiation of human
induced pluripotent stem cells follows developmental principles
but with variable potency. Proc Natl Acad Sci U S A. 2010;107(9):4335-4340.
- 14. Lafaille FG, Pessach IM, Zhang SY, et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS
cells. Nature. 2012;491(7426):769-773.
- 15. Mormone E, D'Sousa S, Alexeeva V, Bederson MM, Germano
IM. "Footprint-free" human induced pluripotent stem cell-derived
astrocytes for in vivo cell-based therapy. Stem Cells Dev.
2014;23(21):2626-2636.
- 16. Le magueresse C, Monyer H. GABAergic interneurons shape
the functional maturation of the cortex. Neuron. 2013;77(3):388-
405.
- 17. Goulburn AL, Stanley EG, Elefanty AG, Anderson SA. Generating
GABAergic cerebral cortical interneurons from mouse and
human embryonic stem cells. Stem Cell Res. 2012;8(3):416-
26.
- 18. Yang N, Chanda S, Marro S, et al. Generation of pure GABAergic
neurons by transcription factor programming. Nat Methods.
2017;14(6):621-628.
- 19. Gonzalez-Ramos A, Waloschková E, Mikroulis A, Kokaia Z,
Bengzon J, Ledri M, Andersson M, Kokaia M. Human stem
cell-derived GABAergic neurons functionally integrate into human
neuronal networks. Sci Rep. 2021;11(1):22050.
- 20. Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC. Directed
differentiation of forebrain GABA interneurons from human
pluripotent stem cells. Nat Protoc. 2013;8(9):1670-9.
- 21. Sun AX, Yuan Q, Tan S, Xiao Y, Wang D, Khoo AT, Sani L, Tran
HD, Kim P, Chiew YS, Lee KJ, Yen YC, Ng HH, Lim B, Je HS.
Direct Induction and Functional Maturation of Forebrain GABAergic
Neurons from Human Pluripotent Stem Cells. Cell Rep.
2016;16(7):1942-53.
- 22. Goldman SA, Kuypers NJ. How to make an oligodendrocyte.
Development. 2015;142(23):3983-3995.
- 23. Bradl M, Lassmann H. Oligodendrocytes: biology and pathology.
Acta Neuropathol. 2010;119(1):37-53.
- 24. Li L, Chao J, Shi Y. Modeling neurological diseases using iPSC-
derived neural cells : iPSC modeling of neurological diseases.
Cell Tissue Res. 2018;371(1):143-151.
- 25. Ehrlich M, Mozafari S, Glatza M, Starost L, Velychko S, Hallmann
AL, Cui QL, Schambach A, Kim KP, Bachelin C, Marteyn
A, Hargus G, Johnson RM, Antel J, Sterneckert J, Zaehres H,
Schöler HR, Baron-Van Evercooren A, Kuhlmann T. Rapid and
efficient generation of oligodendrocytes from human induced
pluripotent stem cells using transcription factors. Proc Natl
Acad Sci U S A. 2017;114(11):E2243-E2252.
- 26. Shaker MR, Pietrogrande G, Martin S, Lee JH, Sun W, Wolvetang
EJ. Rapid and Efficient Generation of Myelinating
Human Oligodendrocytes in Organoids. Front Cell Neurosci.
2021;15:631548.
- 27. Qu Q, Li D, Louis KR, et al. High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1. Nat Commun. 2014;5:3449.
- 28. Bianchi F, Malboubi M, Li Y, et al. Rapid and efficient differentiation of functional motor neurons from human iPSC for neural injury modelling. Stem Cell Res. 2018;32:126-134.
- 29. Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey
MR, Lowry E, Macklis JD, Rushton D, Sadegh C, Sareen
D, Wichterle H, Zhang SC, Svendsen CN. Modeling ALS with
motor neurons derived from human induced pluripotent stem
cells. Nat Neurosci. 2016;19(4):542-53.
- 30. Osaki T, Uzel SGM, Kamm RD. Microphysiological 3D model
of amyotrophic lateral sclerosis (ALS) from human iPS-derived
muscle cells and optogenetic motor neurons. Sci Adv.
2018;4(10):eaat5847.
- 31. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human
ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol.
2009;27(3):275-80.
- 32. Li W, Sun W, Zhang Y, et al. Rapid induction and long-term self-
renewal of primitive neural precursors from human embryonic
stem cells by small molecule inhibitors. Proc Natl Acad Sci U S
A. 2011;108(20):8299–8304.
METHODS OF DIFFERENTIATION FROM PLURIPOTENT STEM CELLS TO NEURAL CELLS
Year 2022,
Volume: 29 Issue: 4, 691 - 696, 27.12.2022
Meltem Kuruş
,
Kemal Ergin
,
Rahmi Çetinkaya
Abstract
Human embryonic stem cells are derived from inner
cell mass of early stage blastocyst embryos. These
cells are pluripotent and can differentiate into functional
neurons and various nerve cells under appropriate
conditions. However, one of the biggest challenges in
this area is to establish a renewable, easy-to-culture,
neural lineage-linked neural precursor cell population.
Therefore, it is crucial to conveniently differentiate
human embryonic stem cells into precursor cells,
maintain them as a self-renewing population, and
achieve nerve cell types from different regions as a
pure population. Cell signals and their associated
molecules also play an important role in these events.
For the generation of neural precursor cells, a better
understanding of stem cell biology and the important
pathways involved in differentiation into neural cells
is required. This review focuses on the differentiation
methods from stem cells to neural cells and the
important signaling pathways and molecules in this
process.
Project Number
2016-ÖNP-TIPF-0028
References
- 1. Liu G, David BT, Trawczynski M, Fessler RG. Advances in Pluripotent
Stem Cells: History, Mechanisms, Technologies, and Applications. Stem Cell Rev Rep. 2020;16(1):3-32.
- 2. Zhang S, Bell E, Zhi H, Brown S, Imran SAM, Azuara V, Cui W.
OCT4 and PAX6 determine the dual function of SOX2 in human
ESCs as a key pluripotent or neural factor. Stem Cell Res Ther.
2019;10(1):122.
- 3. Elkabetz Y, Panagiotakos G, Al Shamy G, Socci ND, Tabar
V, Studer L. Human ES cell-derived neural rosettes reveal a
functionally distinct early neural stem cell stage. Genes Dev.
2008;22(2):152-65.
- 4. Selvaraj V, Jiang P, Chechneva O, Lo UG, Deng W. Differentiating
human stem cells into neurons and glial cells for neural
repair. Front Biosci (Landmark Ed). 2012;17:65-89.
- 5. Perrier AL, Tabar V, Barberi T, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl
Acad Sci USA. 2004;101(34):12543-8.
- 6. Mizuseki K, Sakamoto T, Watanabe K, Muguruma K, Ikeya
M, Nishiyama A, Arakawa A, Suemori H, Nakatsuji N, Kawasaki
H, Murakami F, Sasai Y. Generation of neural crest-derived
peripheral neurons and floor plate cells from mouse
and primate embryonic stem cells. Proc Natl Acad Sci U S A.
2003;100(10):5828-33.
- 7. Roy NS, Cleren C, Singh SK, Yang L, Beal MF, Goldman
SA.(2006) Functional engraftment of human ES cell-derived
dopaminergic neurons enriched by coculture with telomerase-
immortalized midbrain astrocytes Nat Med 12, 1259–68.
- 8. Yang D, Zhang ZJ, Oldenburg M, Ayala M, Zhang SC. Human
embryonic stem cell-derived dopaminergic neurons
reverse functional deficit in parkinsonian rats. Stem Cells.
2008;26(1):55-63.
- 9. Pekny M, Pekna M, Messing A, et al. Astrocytes: a central
element in neurological diseases. Acta Neuropathol.
2016;131(3):323-345.
- 10. Krencik R, Zhang SC. Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc.
2011;6(11):1710-1717.
- 11. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M,
Sadelain M, Studer L. Highly efficient neural conversion of
human ES and iPS cells by dual inhibition of SMAD signaling
[published correction appears in Nat Biotechnol. 2009
May;27(5):485]. Nat Biotechnol. 2009;27(3):275-280.
- 12. Zhang SC, Wernig M, Duncan ID, Brüstle O, Thomson JA. In
vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001;19(12):1129-
1133.
- 13. Hu BY, Weick JP, Yu J, et al. Neural differentiation of human
induced pluripotent stem cells follows developmental principles
but with variable potency. Proc Natl Acad Sci U S A. 2010;107(9):4335-4340.
- 14. Lafaille FG, Pessach IM, Zhang SY, et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS
cells. Nature. 2012;491(7426):769-773.
- 15. Mormone E, D'Sousa S, Alexeeva V, Bederson MM, Germano
IM. "Footprint-free" human induced pluripotent stem cell-derived
astrocytes for in vivo cell-based therapy. Stem Cells Dev.
2014;23(21):2626-2636.
- 16. Le magueresse C, Monyer H. GABAergic interneurons shape
the functional maturation of the cortex. Neuron. 2013;77(3):388-
405.
- 17. Goulburn AL, Stanley EG, Elefanty AG, Anderson SA. Generating
GABAergic cerebral cortical interneurons from mouse and
human embryonic stem cells. Stem Cell Res. 2012;8(3):416-
26.
- 18. Yang N, Chanda S, Marro S, et al. Generation of pure GABAergic
neurons by transcription factor programming. Nat Methods.
2017;14(6):621-628.
- 19. Gonzalez-Ramos A, Waloschková E, Mikroulis A, Kokaia Z,
Bengzon J, Ledri M, Andersson M, Kokaia M. Human stem
cell-derived GABAergic neurons functionally integrate into human
neuronal networks. Sci Rep. 2021;11(1):22050.
- 20. Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC. Directed
differentiation of forebrain GABA interneurons from human
pluripotent stem cells. Nat Protoc. 2013;8(9):1670-9.
- 21. Sun AX, Yuan Q, Tan S, Xiao Y, Wang D, Khoo AT, Sani L, Tran
HD, Kim P, Chiew YS, Lee KJ, Yen YC, Ng HH, Lim B, Je HS.
Direct Induction and Functional Maturation of Forebrain GABAergic
Neurons from Human Pluripotent Stem Cells. Cell Rep.
2016;16(7):1942-53.
- 22. Goldman SA, Kuypers NJ. How to make an oligodendrocyte.
Development. 2015;142(23):3983-3995.
- 23. Bradl M, Lassmann H. Oligodendrocytes: biology and pathology.
Acta Neuropathol. 2010;119(1):37-53.
- 24. Li L, Chao J, Shi Y. Modeling neurological diseases using iPSC-
derived neural cells : iPSC modeling of neurological diseases.
Cell Tissue Res. 2018;371(1):143-151.
- 25. Ehrlich M, Mozafari S, Glatza M, Starost L, Velychko S, Hallmann
AL, Cui QL, Schambach A, Kim KP, Bachelin C, Marteyn
A, Hargus G, Johnson RM, Antel J, Sterneckert J, Zaehres H,
Schöler HR, Baron-Van Evercooren A, Kuhlmann T. Rapid and
efficient generation of oligodendrocytes from human induced
pluripotent stem cells using transcription factors. Proc Natl
Acad Sci U S A. 2017;114(11):E2243-E2252.
- 26. Shaker MR, Pietrogrande G, Martin S, Lee JH, Sun W, Wolvetang
EJ. Rapid and Efficient Generation of Myelinating
Human Oligodendrocytes in Organoids. Front Cell Neurosci.
2021;15:631548.
- 27. Qu Q, Li D, Louis KR, et al. High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1. Nat Commun. 2014;5:3449.
- 28. Bianchi F, Malboubi M, Li Y, et al. Rapid and efficient differentiation of functional motor neurons from human iPSC for neural injury modelling. Stem Cell Res. 2018;32:126-134.
- 29. Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey
MR, Lowry E, Macklis JD, Rushton D, Sadegh C, Sareen
D, Wichterle H, Zhang SC, Svendsen CN. Modeling ALS with
motor neurons derived from human induced pluripotent stem
cells. Nat Neurosci. 2016;19(4):542-53.
- 30. Osaki T, Uzel SGM, Kamm RD. Microphysiological 3D model
of amyotrophic lateral sclerosis (ALS) from human iPS-derived
muscle cells and optogenetic motor neurons. Sci Adv.
2018;4(10):eaat5847.
- 31. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human
ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol.
2009;27(3):275-80.
- 32. Li W, Sun W, Zhang Y, et al. Rapid induction and long-term self-
renewal of primitive neural precursors from human embryonic
stem cells by small molecule inhibitors. Proc Natl Acad Sci U S
A. 2011;108(20):8299–8304.