Page 1 of 40
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
1
Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells
Said Assou1,2, Emilie Pourret2, Marie Péquignot3, Valérie Rigau4, Vasiliki Kalatzis3, Ounissa Aït-Ahmed2,§, Samir Hamamah1,2,5, §*
1
Université MONTPELLIER, UFR de Médecine, Montpellier, France ; 2INSERM U1203,
Institute for Regenerative Medicine and Biotherapy, CHRU Montpellier, Hôpital Saint-Eloi, Montpellier, France ; 3Institut des Neurosciences de Montpellier, INSERM U1051, Hôpital Saint-Eloi, Montpellier ; 4Pathology Department, University Hospital Gui de Chauliac, Montpellier, France ;
5
ART-PGD department, CHU Montpellier, Hôpital Arnaud de
Villeneuve, Montpellier, France.
§
Co-senior authors.
*
to whom correspondence should be addressed
Prof. S. Hamamah, ART/PGD Department, Hôpital Arnaud de Villeneuve, INSERM U1203. Montpellier-34295, France.
Tel: +33 4 67 33 64 04; Fax: +33 4 67 33 62 90. E-mail: [email protected]
Running title : Cumulus derived cells as a feeder
Abstract
Page 2 of 40
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
2 Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CCs niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells (hiPSCs). The iPS cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (p15)
Gene ID Gene Name UniGene ID Gene Title Chromosomal Fold Location change q-value(%) 203824_at TSPAN8 Hs.170563 tetraspanin 8 chr12q14.1-q21.1 467.951526892218 3.08729644234173 224588_at XIST Hs.529901 X (inactive)-specific chrXq13.2 transcript280.149916002976 3.08729644234173 201641_at BST2 Hs.118110 bone marrow stromal chr19p13.2 cell antigen 188.195511718903 2 3.08729644234173 219263_at RNF128 Hs.496542 ring finger protein chrXq22.3 128 185.6765896464 3.08729644234173 209821_at C9orf26 Hs.348390 interleukin 33 chr9p24.1 184.052102236534 3.08729644234173 205113_at NEF3 Hs.458657 neurofilament, medium chr8p21polypeptide 159.998037387658 150kDa 3.08729644234173 204548_at STAR Hs.521535 steroidogenic acute chr8p11.2 regulator119.222180623636 3.08729644234173 205159_at CSF2RB Hs.592192 colony stimulating chr22q13.1 factor 2 receptor, 116.702460984273 beta, 3.08729644234173 low-affinity (granulocyte-macrophage) /// co 205969_at AADAC Hs.506908 arylacetamide deacetylase chr3q21.3-q25.2 (esterase) 107.424586657845 3.08729644234173 1561969_at ZPLD1 Hs.352213 zona pellucida-like chr3q12.3 domain containing 101.478773918449 1 3.08729644234173 221805_at NEFL Hs.521461 neurofilament, light chr8p21 polypeptide 91.6092606249348 68kDa 3.08729644234173 231947_at MYCT1 Hs.18160 myc target 1 chr6q25.2 91.0704997052397 3.08729644234173 205404_at HSD11B1 Hs.195040 hydroxysteroid (11-beta) chr1q32-q4179.2046544679622 dehydrogenase3.08729644234173 1 209583_s_atCD200 Hs.79015 CD200 molecule chr3q12-q1369.9596530611367 3.08729644234173 203868_s_atVCAM1 Hs.109225 vascular cell adhesion chr1p32-p3169.2388397619457 molecule 1 3.08729644234173 206018_at FOXG1B Hs.632336 forkhead box G1Bchr14q12-q13 69.1868217478426 3.08729644234173 230081_at PLCXD3 Hs.145404 phosphatidylinositol-specific chr5p13.1 phospholipase 65.4076429189212 3.08729644234173 C, X domain containing 3 205476_at CCL20 Hs.75498 chemokine (C-C motif) chr2q33-q3764.7589943793112 ligand 20 3.08729644234173 217028_at CXCR4 Hs.593413 chemokine (C-X-Cchr2q21 motif) receptor 51.2084682598439 4 3.08729644234173 207103_at KCND2 Hs.21703 potassium voltage-gated chr7q31 channel, 48.9654563715517 Shal-related 3.08729644234173 subfamily, member 2 204309_at CYP11A1 Hs.303980 cytochrome P450, chr15q23-q24 family 11, subfamily 44.485607426434 A, 3.08729644234173 polypeptide 1 /// cytochrome P450, family 11 208209_s_atC4BPB Hs.99886 complement component chr1q32 4 binding 41.4582239011503 protein, 3.08729644234173 beta 209823_x_atHLA-DQB1Hs.409934 major histocompatibility chr6p21.3 complex, 36.7414411718917 class 3.08729644234173 II, DQ beta 1 204882_at ARHGAP25Hs.531807 Rho GTPase activating chr2p14 protein36.6951163001689 25 3.08729644234173 228708_at RAB27B Hs.20961 ///RAB27B, Hs.25318 memberchr18q21.2 RAS oncogene /// 32.4093567874234 chr7p22.3 family /// 3.08729644234173 G protein-coupled receptor 30 213524_s_atG0S2 Hs.432132 G0/G1switch 2 chr1q32.2-q41 31.6627786763061 3.08729644234173 206022_at NDP Hs.522615 Norrie disease (pseudoglioma) chrXp11.4 30.3873381412097 3.08729644234173 213618_at CENTD1 Hs.479451 centaurin, delta 1chr4p14 29.2980615607671 3.08729644234173 225645_at EHF Hs.502306 Ets homologous factor chr11p12 28.8909345848959 3.08729644234173 1556209_at CLEC2B Hs.85201 C-type lectin domain chr12p13-p12 family 2,28.7297699234648 member B3.08729644234173 1558668_s_at SPATA22 Hs.351068 spermatogenesischr17p13.3 associated 22 27.8644572478344 3.08729644234173 239155_at LOC653108 Hs.647457 similar to coxsackie chr21q11.2 virus and 27.2004104108233 adenovirus3.08729644234173 receptor precursor /// similar to coxsackie vir 206569_at IL24 Hs.642714 interleukin 24 chr1q32 27.0536803987797 3.08729644234173 226374_at CXADR Hs.634837 Coxsackie virus and chr21q21.1 adenovirus 26.364403006927 receptor3.08729644234173 235527_at LOC284214 Hs.594640 hypothetical protein chr18p11.3124.8683184000998 LOC284214 3.08729644234173 221085_at TNFSF15 Hs.241382 tumor necrosis factor chr9q32 (ligand)23.9381719641795 superfamily, 3.08729644234173 member 15 208606_s_atWNT4 Hs.591521 wingless-type MMTV chr1p36.23-p35.1 integration 22.8788754731063 site family, 3.08729644234173 member 4 /// wingless-type MMTV integr 229686_at P2RY8 Hs.111377 purinergic receptor chrXp22.33; P2Y, G-protein 21.5445918807733 Yp11.3 coupled, 3.08729644234173 8 215161_at CAMK1G Hs.199068 calcium/calmodulin-dependent chr1q32-q4121.4248640592197 protein kinase 3.08729644234173 IG 205517_at GATA4 Hs.243987 GATA binding protein chr8p23.1-p22 4 21.254443184103 3.08729644234173 219804_at SYNPO2L Hs.645273 synaptopodin 2-like chr10q22.2 21.150408763413 3.08729644234173 201340_s_atENC1 Hs.104925 ectodermal-neural chr5q12-q13.3 cortex (with 20.5115492725827 BTB-like3.08729644234173 domain) 202859_x_atIL8 Hs.624 interleukin 8 chr4q13-q2120.3892886176085 3.08729644234173 209993_at ABCB1 Hs.489033 ATP-binding cassette, chr7q21.1 sub-family 19.6140988711148 B (MDR/TAP), 3.08729644234173 member 1 204971_at CSTA Hs.518198 cystatin A (stefin chr3q21 A) 17.6216633140211 3.08729644234173 212592_at IGJ Hs.651109 Immunoglobulin chr4q21 J polypeptide, 17.6100761539264 linker protein 3.08729644234173 for immunoglobulin alpha and mu polype
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
209570_s_atD4S234E 237466_s_atHHIP 209277_at TFPI2 227190_at TMEM37
Hs.518595 Hs.507991 Hs.438231 Hs.26216
DNA segment onchr4p16.3 chromosome 16.7392626214 4 (unique) 3.08729644234173 234 expressed sequence hedgehog interacting chr4q28-q3216.3670953867456 protein 3.08729644234173 tissue factor pathway chr7q22 inhibitor 15.8308665575102 2 3.08729644234173 transmembrane protein chr2q14.2 37 15.5642405954571 3.08729644234173
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Supplementary Table S6 List of over-expressed transcripts that were represented in Venn diagram Part 1/3: List of the 722 transcripts ProbeSet 221805_at 205113_at 231947_at 1561969_at 229242_at 203824_at 206969_at 208712_at 219134_at 223395_at 206298_at 223672_at 204614_at 218451_at 222862_s_at 239650_at 219308_s_at 228564_at 219804_at 214841_at 230250_at 228438_at 204682_at 235236_at 206569_at 228708_at 208483_x_at 243313_at 1555673_at 202036_s_at 1553994_at 232122_s_at 210078_s_at 209789_at 231781_s_at 208209_s_at 237159_x_at 228360_at 203476_at 235664_at 231867_at 230240_at 209821_at 219263_at 230943_at 203868_s_at 201641_at
Name NEFL NEF3 MYCT1 ZPLD1 Hs.23349 TSPAN8 KRTHA4 CCND1 ELTD1 ABI3BP ARHGAP22 SGIP1 SERPINB2 CDCP1 AK5 NAP5 AK5 LOC375295 SYNPO2L CNIH3 PTPRB TRPA1 LTBP2 DOCK2 IL24 RAB27B KRTHA3A SYNPO2L KRTAP2P1 SFRP1 NT5E VEPH1 KCNAB1 CORO2B LRRC2 C4BPB AP1S3 LOC130576 TPBG GPR177 ODZ2 DYRK3 C9orf26 RNF128 Hs.599590 VCAM1 BST2
UniGene/ID Hs.521461 Hs.458657 Hs.18160 Hs.352213 Hs.23349 Hs.170563 Hs.296942 Hs.523852 Hs.132314 Hs.477015 Hs.435063 Hs.132121 Hs.594481 Hs.476093 Hs.559718
Gene/Title Chromosomal/Location neurofilament,
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
1
Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells
Said Assou1,2, Emilie Pourret2, Marie Péquignot3, Valérie Rigau4, Vasiliki Kalatzis3, Ounissa Aït-Ahmed2,§, Samir Hamamah1,2,5, §*
1
Université MONTPELLIER, UFR de Médecine, Montpellier, France ; 2INSERM U1203,
Institute for Regenerative Medicine and Biotherapy, CHRU Montpellier, Hôpital Saint-Eloi, Montpellier, France ; 3Institut des Neurosciences de Montpellier, INSERM U1051, Hôpital Saint-Eloi, Montpellier ; 4Pathology Department, University Hospital Gui de Chauliac, Montpellier, France ;
5
ART-PGD department, CHU Montpellier, Hôpital Arnaud de
Villeneuve, Montpellier, France.
§
Co-senior authors.
*
to whom correspondence should be addressed
Prof. S. Hamamah, ART/PGD Department, Hôpital Arnaud de Villeneuve, INSERM U1203. Montpellier-34295, France.
Tel: +33 4 67 33 64 04; Fax: +33 4 67 33 62 90. E-mail: [email protected]
Running title : Cumulus derived cells as a feeder
Abstract
Page 2 of 40
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
2 Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CCs niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells (hiPSCs). The iPS cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (p15)
Gene ID Gene Name UniGene ID Gene Title Chromosomal Fold Location change q-value(%) 203824_at TSPAN8 Hs.170563 tetraspanin 8 chr12q14.1-q21.1 467.951526892218 3.08729644234173 224588_at XIST Hs.529901 X (inactive)-specific chrXq13.2 transcript280.149916002976 3.08729644234173 201641_at BST2 Hs.118110 bone marrow stromal chr19p13.2 cell antigen 188.195511718903 2 3.08729644234173 219263_at RNF128 Hs.496542 ring finger protein chrXq22.3 128 185.6765896464 3.08729644234173 209821_at C9orf26 Hs.348390 interleukin 33 chr9p24.1 184.052102236534 3.08729644234173 205113_at NEF3 Hs.458657 neurofilament, medium chr8p21polypeptide 159.998037387658 150kDa 3.08729644234173 204548_at STAR Hs.521535 steroidogenic acute chr8p11.2 regulator119.222180623636 3.08729644234173 205159_at CSF2RB Hs.592192 colony stimulating chr22q13.1 factor 2 receptor, 116.702460984273 beta, 3.08729644234173 low-affinity (granulocyte-macrophage) /// co 205969_at AADAC Hs.506908 arylacetamide deacetylase chr3q21.3-q25.2 (esterase) 107.424586657845 3.08729644234173 1561969_at ZPLD1 Hs.352213 zona pellucida-like chr3q12.3 domain containing 101.478773918449 1 3.08729644234173 221805_at NEFL Hs.521461 neurofilament, light chr8p21 polypeptide 91.6092606249348 68kDa 3.08729644234173 231947_at MYCT1 Hs.18160 myc target 1 chr6q25.2 91.0704997052397 3.08729644234173 205404_at HSD11B1 Hs.195040 hydroxysteroid (11-beta) chr1q32-q4179.2046544679622 dehydrogenase3.08729644234173 1 209583_s_atCD200 Hs.79015 CD200 molecule chr3q12-q1369.9596530611367 3.08729644234173 203868_s_atVCAM1 Hs.109225 vascular cell adhesion chr1p32-p3169.2388397619457 molecule 1 3.08729644234173 206018_at FOXG1B Hs.632336 forkhead box G1Bchr14q12-q13 69.1868217478426 3.08729644234173 230081_at PLCXD3 Hs.145404 phosphatidylinositol-specific chr5p13.1 phospholipase 65.4076429189212 3.08729644234173 C, X domain containing 3 205476_at CCL20 Hs.75498 chemokine (C-C motif) chr2q33-q3764.7589943793112 ligand 20 3.08729644234173 217028_at CXCR4 Hs.593413 chemokine (C-X-Cchr2q21 motif) receptor 51.2084682598439 4 3.08729644234173 207103_at KCND2 Hs.21703 potassium voltage-gated chr7q31 channel, 48.9654563715517 Shal-related 3.08729644234173 subfamily, member 2 204309_at CYP11A1 Hs.303980 cytochrome P450, chr15q23-q24 family 11, subfamily 44.485607426434 A, 3.08729644234173 polypeptide 1 /// cytochrome P450, family 11 208209_s_atC4BPB Hs.99886 complement component chr1q32 4 binding 41.4582239011503 protein, 3.08729644234173 beta 209823_x_atHLA-DQB1Hs.409934 major histocompatibility chr6p21.3 complex, 36.7414411718917 class 3.08729644234173 II, DQ beta 1 204882_at ARHGAP25Hs.531807 Rho GTPase activating chr2p14 protein36.6951163001689 25 3.08729644234173 228708_at RAB27B Hs.20961 ///RAB27B, Hs.25318 memberchr18q21.2 RAS oncogene /// 32.4093567874234 chr7p22.3 family /// 3.08729644234173 G protein-coupled receptor 30 213524_s_atG0S2 Hs.432132 G0/G1switch 2 chr1q32.2-q41 31.6627786763061 3.08729644234173 206022_at NDP Hs.522615 Norrie disease (pseudoglioma) chrXp11.4 30.3873381412097 3.08729644234173 213618_at CENTD1 Hs.479451 centaurin, delta 1chr4p14 29.2980615607671 3.08729644234173 225645_at EHF Hs.502306 Ets homologous factor chr11p12 28.8909345848959 3.08729644234173 1556209_at CLEC2B Hs.85201 C-type lectin domain chr12p13-p12 family 2,28.7297699234648 member B3.08729644234173 1558668_s_at SPATA22 Hs.351068 spermatogenesischr17p13.3 associated 22 27.8644572478344 3.08729644234173 239155_at LOC653108 Hs.647457 similar to coxsackie chr21q11.2 virus and 27.2004104108233 adenovirus3.08729644234173 receptor precursor /// similar to coxsackie vir 206569_at IL24 Hs.642714 interleukin 24 chr1q32 27.0536803987797 3.08729644234173 226374_at CXADR Hs.634837 Coxsackie virus and chr21q21.1 adenovirus 26.364403006927 receptor3.08729644234173 235527_at LOC284214 Hs.594640 hypothetical protein chr18p11.3124.8683184000998 LOC284214 3.08729644234173 221085_at TNFSF15 Hs.241382 tumor necrosis factor chr9q32 (ligand)23.9381719641795 superfamily, 3.08729644234173 member 15 208606_s_atWNT4 Hs.591521 wingless-type MMTV chr1p36.23-p35.1 integration 22.8788754731063 site family, 3.08729644234173 member 4 /// wingless-type MMTV integr 229686_at P2RY8 Hs.111377 purinergic receptor chrXp22.33; P2Y, G-protein 21.5445918807733 Yp11.3 coupled, 3.08729644234173 8 215161_at CAMK1G Hs.199068 calcium/calmodulin-dependent chr1q32-q4121.4248640592197 protein kinase 3.08729644234173 IG 205517_at GATA4 Hs.243987 GATA binding protein chr8p23.1-p22 4 21.254443184103 3.08729644234173 219804_at SYNPO2L Hs.645273 synaptopodin 2-like chr10q22.2 21.150408763413 3.08729644234173 201340_s_atENC1 Hs.104925 ectodermal-neural chr5q12-q13.3 cortex (with 20.5115492725827 BTB-like3.08729644234173 domain) 202859_x_atIL8 Hs.624 interleukin 8 chr4q13-q2120.3892886176085 3.08729644234173 209993_at ABCB1 Hs.489033 ATP-binding cassette, chr7q21.1 sub-family 19.6140988711148 B (MDR/TAP), 3.08729644234173 member 1 204971_at CSTA Hs.518198 cystatin A (stefin chr3q21 A) 17.6216633140211 3.08729644234173 212592_at IGJ Hs.651109 Immunoglobulin chr4q21 J polypeptide, 17.6100761539264 linker protein 3.08729644234173 for immunoglobulin alpha and mu polype
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
209570_s_atD4S234E 237466_s_atHHIP 209277_at TFPI2 227190_at TMEM37
Hs.518595 Hs.507991 Hs.438231 Hs.26216
DNA segment onchr4p16.3 chromosome 16.7392626214 4 (unique) 3.08729644234173 234 expressed sequence hedgehog interacting chr4q28-q3216.3670953867456 protein 3.08729644234173 tissue factor pathway chr7q22 inhibitor 15.8308665575102 2 3.08729644234173 transmembrane protein chr2q14.2 37 15.5642405954571 3.08729644234173
Stem Cells and Development Cultured cells from the human oocyte cumulus niche are efficient feeders to propagate pluripotent stem cells (doi: 10.1089/scd.2015.0043) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Supplementary Table S6 List of over-expressed transcripts that were represented in Venn diagram Part 1/3: List of the 722 transcripts ProbeSet 221805_at 205113_at 231947_at 1561969_at 229242_at 203824_at 206969_at 208712_at 219134_at 223395_at 206298_at 223672_at 204614_at 218451_at 222862_s_at 239650_at 219308_s_at 228564_at 219804_at 214841_at 230250_at 228438_at 204682_at 235236_at 206569_at 228708_at 208483_x_at 243313_at 1555673_at 202036_s_at 1553994_at 232122_s_at 210078_s_at 209789_at 231781_s_at 208209_s_at 237159_x_at 228360_at 203476_at 235664_at 231867_at 230240_at 209821_at 219263_at 230943_at 203868_s_at 201641_at
Name NEFL NEF3 MYCT1 ZPLD1 Hs.23349 TSPAN8 KRTHA4 CCND1 ELTD1 ABI3BP ARHGAP22 SGIP1 SERPINB2 CDCP1 AK5 NAP5 AK5 LOC375295 SYNPO2L CNIH3 PTPRB TRPA1 LTBP2 DOCK2 IL24 RAB27B KRTHA3A SYNPO2L KRTAP2P1 SFRP1 NT5E VEPH1 KCNAB1 CORO2B LRRC2 C4BPB AP1S3 LOC130576 TPBG GPR177 ODZ2 DYRK3 C9orf26 RNF128 Hs.599590 VCAM1 BST2
UniGene/ID Hs.521461 Hs.458657 Hs.18160 Hs.352213 Hs.23349 Hs.170563 Hs.296942 Hs.523852 Hs.132314 Hs.477015 Hs.435063 Hs.132121 Hs.594481 Hs.476093 Hs.559718
Gene/Title Chromosomal/Location neurofilament,
